- About
- Home
- Introduction
- Statistics
- Programs
- Dignet
- Gene
- GenePair
- BioSummarAI
- Help & Docs
- Documents
- Help
- FAQs
- Links
- Acknowledge
- Disclaimer
- Contact Us
Gene Information
Gene symbol: MAPK10
Gene name: mitogen-activated protein kinase 10
HGNC ID: 6872
Synonyms: JNK3, p493F12, p54bSAPK
Related Genes
Related Sentences
| # | PMID | Sentence |
| 1 | 1322500 | Raf-1 activates MAP kinase-kinase. |
| 2 | 1322500 | The normal cellular homologue of the acutely transforming oncogene v-raf is c-raf-1, which encodes a serine/threonine protein kinase that is activated by many extracellular stimuli. |
| 3 | 1322500 | The physiological substrates of the protein c-Raf-1 are unknown. |
| 4 | 1322500 | The mitogen-activated protein (MAP) kinases Erk1 and 2 are also activated by mitogens through phosphorylation of Erk tyrosine and threonine residues catalysed by a protein kinase of relative molecular mass 50,000, MAP kinase-kinase (MAPK-K). |
| 5 | 1322500 | Here we report that MAPK-K as well as Erk1 and 2 are constitutively active in v-raf-transformed cells. |
| 6 | 1322500 | MAPK-K partially purified from v-raf-transformed cells or from mitogen-treated cells can be deactivated by phosphatase 2A. c-Raf-1 purified after mitogen stimulation can reactivate the phosphatase 2A-inactivated MAPK-K over 30-fold in vitro. c-Raf-1 reactivation of MAPK-K coincides with the selective phosphorylation at serine/threonine residues of a polypeptide with M(r) 50,000 which coelutes precisely on cation-exchange chromatography with the MAPK-K activatable by c-Raf-1. |
| 7 | 1322500 | These results indicate that c-Raf-1 is an immediate upstream activator of MAPK-K in vivo. |
| 8 | 1322500 | To our knowledge, MAPK-K is the first physiological substrate of the c-raf-1 protooncogene product to be identified. |
| 9 | 1322500 | Raf-1 activates MAP kinase-kinase. |
| 10 | 1322500 | The normal cellular homologue of the acutely transforming oncogene v-raf is c-raf-1, which encodes a serine/threonine protein kinase that is activated by many extracellular stimuli. |
| 11 | 1322500 | The physiological substrates of the protein c-Raf-1 are unknown. |
| 12 | 1322500 | The mitogen-activated protein (MAP) kinases Erk1 and 2 are also activated by mitogens through phosphorylation of Erk tyrosine and threonine residues catalysed by a protein kinase of relative molecular mass 50,000, MAP kinase-kinase (MAPK-K). |
| 13 | 1322500 | Here we report that MAPK-K as well as Erk1 and 2 are constitutively active in v-raf-transformed cells. |
| 14 | 1322500 | MAPK-K partially purified from v-raf-transformed cells or from mitogen-treated cells can be deactivated by phosphatase 2A. c-Raf-1 purified after mitogen stimulation can reactivate the phosphatase 2A-inactivated MAPK-K over 30-fold in vitro. c-Raf-1 reactivation of MAPK-K coincides with the selective phosphorylation at serine/threonine residues of a polypeptide with M(r) 50,000 which coelutes precisely on cation-exchange chromatography with the MAPK-K activatable by c-Raf-1. |
| 15 | 1322500 | These results indicate that c-Raf-1 is an immediate upstream activator of MAPK-K in vivo. |
| 16 | 1322500 | To our knowledge, MAPK-K is the first physiological substrate of the c-raf-1 protooncogene product to be identified. |
| 17 | 1380182 | Rapamycin, but not its structural analog FK506, also inhibited the basal and insulin-stimulated activity of the p70 ribosomal protein S6 kinase. |
| 18 | 1380182 | By contrast, insulin stimulation of the p85 Rsk S6 kinase and mitogen-activated protein (MAP) kinase activity were unaffected by drug. |
| 19 | 1380182 | Thus, rapamycin inhibits a signal transduction element that is necessary for the activation of p70 S6 kinase and mitogenesis but unnecessary for activation of p85 Rsk S6 kinase or MAP kinase. |
| 20 | 1380182 | Rapamycin, but not its structural analog FK506, also inhibited the basal and insulin-stimulated activity of the p70 ribosomal protein S6 kinase. |
| 21 | 1380182 | By contrast, insulin stimulation of the p85 Rsk S6 kinase and mitogen-activated protein (MAP) kinase activity were unaffected by drug. |
| 22 | 1380182 | Thus, rapamycin inhibits a signal transduction element that is necessary for the activation of p70 S6 kinase and mitogenesis but unnecessary for activation of p85 Rsk S6 kinase or MAP kinase. |
| 23 | 1737788 | An array of insulin-activated, proline-directed serine/threonine protein kinases phosphorylate the p70 S6 kinase. |
| 24 | 1737788 | This study characterizes the insulin-activated serine/threonine protein kinases in H4 hepatoma cells active on a 37-residue synthetic peptide (called the SKAIPS peptide) corresponding to a putative autoinhibitory domain in the carboxyl-terminal tail of the p70 S6 kinase as well as on recombinant p70 S6 kinase. |
| 25 | 1737788 | Three peaks of insulin-stimulated protein kinase active on both these substrates are identified as two (possibly three) isoforms of the 40-45-kDa erk/microtubule-associated protein (MAP)-2 kinase family and a 150-kDa form of cdc2. |
| 26 | 1737788 | Although distinguishable in their substrate specificity, these protein kinases together with the p54 MAP-2 kinase share a major common specificity determinant reflected in the SKAIPS peptide: the requirement for a proline residue immediately carboxyl-terminal to the site of Ser/Thr phosphorylation. |
| 27 | 1737788 | In addition, however, at least one peak of insulin-stimulated protein kinase active on recombinant p70, but not on the SKAIPS peptide, is present although not yet identified. |
| 28 | 1737788 | MFP/cdc2 phosphorylates both rat liver p70 S6 kinase and recombinant p70 S6 kinase exclusively at a set of Ser/Thr residues within the putative autoinhibitory (SKAIPS peptide) domain. erk/MAP kinase does not phosphorylate rat liver p70 S6 kinase, but readily phosphorylates recombinant p70 S6 kinase at sites both within and in addition to those encompassed by the SKAIPS peptide sequences. |
| 29 | 1737788 | Although the tryptic 32P-peptides bearing the cdc2 and erk/MAP kinase phosphorylation sites co-migrate with a subset of the sites phosphorylated in situ in insulin-stimulated cells, phosphorylation of the p70 S6 kinase by these proline-directed protein kinases in vitro does not reproducibly activate p70 S6 kinase activity. |
| 30 | 1737788 | Thus, one or more erk/MAP kinases and cdc2 are likely to participate in the insulin-induced phosphorylation of the p70 S6 kinase. |
| 31 | 1737788 | In addition to these kinases, however, phosphorylation of the p70 S6 kinase by other as yet unidentified protein kinases is necessary to recapitulate the multisite phosphorylation required for activation of the p70 S6 kinase. |
| 32 | 1737788 | An array of insulin-activated, proline-directed serine/threonine protein kinases phosphorylate the p70 S6 kinase. |
| 33 | 1737788 | This study characterizes the insulin-activated serine/threonine protein kinases in H4 hepatoma cells active on a 37-residue synthetic peptide (called the SKAIPS peptide) corresponding to a putative autoinhibitory domain in the carboxyl-terminal tail of the p70 S6 kinase as well as on recombinant p70 S6 kinase. |
| 34 | 1737788 | Three peaks of insulin-stimulated protein kinase active on both these substrates are identified as two (possibly three) isoforms of the 40-45-kDa erk/microtubule-associated protein (MAP)-2 kinase family and a 150-kDa form of cdc2. |
| 35 | 1737788 | Although distinguishable in their substrate specificity, these protein kinases together with the p54 MAP-2 kinase share a major common specificity determinant reflected in the SKAIPS peptide: the requirement for a proline residue immediately carboxyl-terminal to the site of Ser/Thr phosphorylation. |
| 36 | 1737788 | In addition, however, at least one peak of insulin-stimulated protein kinase active on recombinant p70, but not on the SKAIPS peptide, is present although not yet identified. |
| 37 | 1737788 | MFP/cdc2 phosphorylates both rat liver p70 S6 kinase and recombinant p70 S6 kinase exclusively at a set of Ser/Thr residues within the putative autoinhibitory (SKAIPS peptide) domain. erk/MAP kinase does not phosphorylate rat liver p70 S6 kinase, but readily phosphorylates recombinant p70 S6 kinase at sites both within and in addition to those encompassed by the SKAIPS peptide sequences. |
| 38 | 1737788 | Although the tryptic 32P-peptides bearing the cdc2 and erk/MAP kinase phosphorylation sites co-migrate with a subset of the sites phosphorylated in situ in insulin-stimulated cells, phosphorylation of the p70 S6 kinase by these proline-directed protein kinases in vitro does not reproducibly activate p70 S6 kinase activity. |
| 39 | 1737788 | Thus, one or more erk/MAP kinases and cdc2 are likely to participate in the insulin-induced phosphorylation of the p70 S6 kinase. |
| 40 | 1737788 | In addition to these kinases, however, phosphorylation of the p70 S6 kinase by other as yet unidentified protein kinases is necessary to recapitulate the multisite phosphorylation required for activation of the p70 S6 kinase. |
| 41 | 7485483 | These include altered expression of insulin-regulated genes such as glucose-6-phosphatase (G-6-Pase), phosphoenolpyruvate carboxykinase (PEPCK), and beta-actin, and genes such as CL-6 and map kinase phosphatase-1 (MKP-1) that were previously unlinked to insulin action in animals. |
| 42 | 7485483 | Abnormal elevation of mRNAs encoding G-6-Pase, MKP-1, and PEPCK in the time 0 diabetic liver results in decreased induction after partial hepatectomy. |
| 43 | 7485483 | Other genes, such as CL-6 and beta-actin, are induced at a lower level in the hepatectomized diabetic animals. |
| 44 | 7556949 | The mitogen-activated protein (MAP) kinases and ribosomal S6 protein kinases in the skeletal muscle of insulin-resistant long-term (2 and 6 months' duration) diabetic rats were investigated to understand further the changes in insulin intracellular signaling pathways that accompany diabetes. |
| 45 | 7556949 | In the insulin-resistant 2-month diabetic rats, the basal activities of MAP kinases were relatively unchanged, while the basal activities of S6 kinases were significantly increased. |
| 46 | 7556949 | Intravenous injection of insulin moderately activated both the 42-kDa MAP kinase (p42mapk) and a 44-kDa MAP kinase (p44erk1) in the 2-month control rats but not in the 2-month diabetic rats. |
| 47 | 7556949 | This correlated with reductions in the amount of immunoreactive p42mapk and p44erk1 proteins in extracts from the diabetic rats. |
| 48 | 7688567 | Regulation of an epitope-tagged recombinant Rsk-1 S6 kinase by phorbol ester and erk/MAP kinase. |
| 49 | 7688567 | Phosphorylation of basal or phosphatase-2A-treated recombinant Rsk-1 in vitro with erk2/MAP kinase increases Rsk-1 40S kinase, peptide kinase, and autophosphorylating activity, retards migration of Rsk-1 polypeptides on SDS-PAGE, and generates new sites of Rsk-1 autophosphorylation in vitro. |
| 50 | 7688567 | By contrast, TPA-activated Rsk-1 is not altered in these properties by phosphorylation in vitro with erk2/MAP kinase. |
| 51 | 7688567 | Activation of Rsk-1 in situ with TPA diminishes by over 90% the extent of Rsk-1 phosphorylation achieved in vitro by erk2/MAP kinase, as compared to the parallel phosphorylation of a phosphatase-2A-treated Rsk-1; basal Rsk-1 is intermediate. |
| 52 | 7688567 | Peptide maps of phosphatase-2A-treated Rsk-1 after phosphorylation in vitro with erk2/MAP kinase exhibit 32P-peptides that comigrate with nearly all of the 32P-peptides present in TPA-activated-32P Rsk-1 labeled in situ, plus several 32P-peptides characteristic of Rsk-1 autophosphorylation in vitro. |
| 53 | 7688567 | Regulation of an epitope-tagged recombinant Rsk-1 S6 kinase by phorbol ester and erk/MAP kinase. |
| 54 | 7688567 | Phosphorylation of basal or phosphatase-2A-treated recombinant Rsk-1 in vitro with erk2/MAP kinase increases Rsk-1 40S kinase, peptide kinase, and autophosphorylating activity, retards migration of Rsk-1 polypeptides on SDS-PAGE, and generates new sites of Rsk-1 autophosphorylation in vitro. |
| 55 | 7688567 | By contrast, TPA-activated Rsk-1 is not altered in these properties by phosphorylation in vitro with erk2/MAP kinase. |
| 56 | 7688567 | Activation of Rsk-1 in situ with TPA diminishes by over 90% the extent of Rsk-1 phosphorylation achieved in vitro by erk2/MAP kinase, as compared to the parallel phosphorylation of a phosphatase-2A-treated Rsk-1; basal Rsk-1 is intermediate. |
| 57 | 7688567 | Peptide maps of phosphatase-2A-treated Rsk-1 after phosphorylation in vitro with erk2/MAP kinase exhibit 32P-peptides that comigrate with nearly all of the 32P-peptides present in TPA-activated-32P Rsk-1 labeled in situ, plus several 32P-peptides characteristic of Rsk-1 autophosphorylation in vitro. |
| 58 | 7688567 | Regulation of an epitope-tagged recombinant Rsk-1 S6 kinase by phorbol ester and erk/MAP kinase. |
| 59 | 7688567 | Phosphorylation of basal or phosphatase-2A-treated recombinant Rsk-1 in vitro with erk2/MAP kinase increases Rsk-1 40S kinase, peptide kinase, and autophosphorylating activity, retards migration of Rsk-1 polypeptides on SDS-PAGE, and generates new sites of Rsk-1 autophosphorylation in vitro. |
| 60 | 7688567 | By contrast, TPA-activated Rsk-1 is not altered in these properties by phosphorylation in vitro with erk2/MAP kinase. |
| 61 | 7688567 | Activation of Rsk-1 in situ with TPA diminishes by over 90% the extent of Rsk-1 phosphorylation achieved in vitro by erk2/MAP kinase, as compared to the parallel phosphorylation of a phosphatase-2A-treated Rsk-1; basal Rsk-1 is intermediate. |
| 62 | 7688567 | Peptide maps of phosphatase-2A-treated Rsk-1 after phosphorylation in vitro with erk2/MAP kinase exhibit 32P-peptides that comigrate with nearly all of the 32P-peptides present in TPA-activated-32P Rsk-1 labeled in situ, plus several 32P-peptides characteristic of Rsk-1 autophosphorylation in vitro. |
| 63 | 7688567 | Regulation of an epitope-tagged recombinant Rsk-1 S6 kinase by phorbol ester and erk/MAP kinase. |
| 64 | 7688567 | Phosphorylation of basal or phosphatase-2A-treated recombinant Rsk-1 in vitro with erk2/MAP kinase increases Rsk-1 40S kinase, peptide kinase, and autophosphorylating activity, retards migration of Rsk-1 polypeptides on SDS-PAGE, and generates new sites of Rsk-1 autophosphorylation in vitro. |
| 65 | 7688567 | By contrast, TPA-activated Rsk-1 is not altered in these properties by phosphorylation in vitro with erk2/MAP kinase. |
| 66 | 7688567 | Activation of Rsk-1 in situ with TPA diminishes by over 90% the extent of Rsk-1 phosphorylation achieved in vitro by erk2/MAP kinase, as compared to the parallel phosphorylation of a phosphatase-2A-treated Rsk-1; basal Rsk-1 is intermediate. |
| 67 | 7688567 | Peptide maps of phosphatase-2A-treated Rsk-1 after phosphorylation in vitro with erk2/MAP kinase exhibit 32P-peptides that comigrate with nearly all of the 32P-peptides present in TPA-activated-32P Rsk-1 labeled in situ, plus several 32P-peptides characteristic of Rsk-1 autophosphorylation in vitro. |
| 68 | 7688567 | Regulation of an epitope-tagged recombinant Rsk-1 S6 kinase by phorbol ester and erk/MAP kinase. |
| 69 | 7688567 | Phosphorylation of basal or phosphatase-2A-treated recombinant Rsk-1 in vitro with erk2/MAP kinase increases Rsk-1 40S kinase, peptide kinase, and autophosphorylating activity, retards migration of Rsk-1 polypeptides on SDS-PAGE, and generates new sites of Rsk-1 autophosphorylation in vitro. |
| 70 | 7688567 | By contrast, TPA-activated Rsk-1 is not altered in these properties by phosphorylation in vitro with erk2/MAP kinase. |
| 71 | 7688567 | Activation of Rsk-1 in situ with TPA diminishes by over 90% the extent of Rsk-1 phosphorylation achieved in vitro by erk2/MAP kinase, as compared to the parallel phosphorylation of a phosphatase-2A-treated Rsk-1; basal Rsk-1 is intermediate. |
| 72 | 7688567 | Peptide maps of phosphatase-2A-treated Rsk-1 after phosphorylation in vitro with erk2/MAP kinase exhibit 32P-peptides that comigrate with nearly all of the 32P-peptides present in TPA-activated-32P Rsk-1 labeled in situ, plus several 32P-peptides characteristic of Rsk-1 autophosphorylation in vitro. |
| 73 | 7822300 | Stimulation of protein phosphatase-1 activity by insulin in rat adipocytes. |
| 74 | 7822300 | In this study, we examined the distribution of protein serine/threonine phosphatase-1 (PP-1) and analyzed the effect of insulin on PP-1 and its mechanism of activation in freshly isolated rat adipocytes. |
| 75 | 7822300 | The adipocyte particulate fraction (PF) constituted approximately 80% of cellular PP-1 activity, while PP-2A was entirely cytosolic. |
| 76 | 7822300 | Insulin rapidly stimulated PF PP-1 in a time- and dose-dependent manner (maximum stimulation at 5 min with 4 nM insulin). |
| 77 | 7822300 | Immunoprecipitation of PF with an antibody against the site-1 sequence of rabbit skeletal muscle glycogen-associated PP-1 (PP-1G) subunit indicated that approximately 40% of adipocyte PP-1 activity was due to PP-1G form of the enzyme. |
| 78 | 7822300 | Insulin stimulated PP-1G (120% over basal levels) without affecting the other forms of PP-1 in the PF. |
| 79 | 7822300 | Insulin activation of PP-1 was accompanied by > 2-fold increase in the phosphorylation state of the 160-kDa regulatory subunit of PP-1. |
| 80 | 7822300 | Stimulation of p21Ras/mitogen-activated protein kinase pathway (MAP) with GTP analogues also resulted in stimulation of PP-1 similar to insulin. |
| 81 | 7822300 | The insulin effect on MAP kinase and PP-1 activation was blocked by a GTP antagonist, guanyl-5'-yl thiophosphate. |
| 82 | 7822300 | The inhibitors of MAP kinase activation (viz. cAMP agonists, SpcAMP and ML-9) also blocked PP-1 stimulation by insulin. |
| 83 | 7822300 | The time course of MAP kinase activation preceded the phosphorylation of PP-1 regulatory subunit and PP-1 activation. |
| 84 | 7822300 | We conclude that insulin rapidly activates a membrane-associated PP-1 in adipocytes, which may be similar to rabbit skeletal muscle PP-1G, and the activation is mediated by p21Ras/MAP kinase pathway. |
| 85 | 7822300 | Stimulation of protein phosphatase-1 activity by insulin in rat adipocytes. |
| 86 | 7822300 | In this study, we examined the distribution of protein serine/threonine phosphatase-1 (PP-1) and analyzed the effect of insulin on PP-1 and its mechanism of activation in freshly isolated rat adipocytes. |
| 87 | 7822300 | The adipocyte particulate fraction (PF) constituted approximately 80% of cellular PP-1 activity, while PP-2A was entirely cytosolic. |
| 88 | 7822300 | Insulin rapidly stimulated PF PP-1 in a time- and dose-dependent manner (maximum stimulation at 5 min with 4 nM insulin). |
| 89 | 7822300 | Immunoprecipitation of PF with an antibody against the site-1 sequence of rabbit skeletal muscle glycogen-associated PP-1 (PP-1G) subunit indicated that approximately 40% of adipocyte PP-1 activity was due to PP-1G form of the enzyme. |
| 90 | 7822300 | Insulin stimulated PP-1G (120% over basal levels) without affecting the other forms of PP-1 in the PF. |
| 91 | 7822300 | Insulin activation of PP-1 was accompanied by > 2-fold increase in the phosphorylation state of the 160-kDa regulatory subunit of PP-1. |
| 92 | 7822300 | Stimulation of p21Ras/mitogen-activated protein kinase pathway (MAP) with GTP analogues also resulted in stimulation of PP-1 similar to insulin. |
| 93 | 7822300 | The insulin effect on MAP kinase and PP-1 activation was blocked by a GTP antagonist, guanyl-5'-yl thiophosphate. |
| 94 | 7822300 | The inhibitors of MAP kinase activation (viz. cAMP agonists, SpcAMP and ML-9) also blocked PP-1 stimulation by insulin. |
| 95 | 7822300 | The time course of MAP kinase activation preceded the phosphorylation of PP-1 regulatory subunit and PP-1 activation. |
| 96 | 7822300 | We conclude that insulin rapidly activates a membrane-associated PP-1 in adipocytes, which may be similar to rabbit skeletal muscle PP-1G, and the activation is mediated by p21Ras/MAP kinase pathway. |
| 97 | 7822300 | Stimulation of protein phosphatase-1 activity by insulin in rat adipocytes. |
| 98 | 7822300 | In this study, we examined the distribution of protein serine/threonine phosphatase-1 (PP-1) and analyzed the effect of insulin on PP-1 and its mechanism of activation in freshly isolated rat adipocytes. |
| 99 | 7822300 | The adipocyte particulate fraction (PF) constituted approximately 80% of cellular PP-1 activity, while PP-2A was entirely cytosolic. |
| 100 | 7822300 | Insulin rapidly stimulated PF PP-1 in a time- and dose-dependent manner (maximum stimulation at 5 min with 4 nM insulin). |
| 101 | 7822300 | Immunoprecipitation of PF with an antibody against the site-1 sequence of rabbit skeletal muscle glycogen-associated PP-1 (PP-1G) subunit indicated that approximately 40% of adipocyte PP-1 activity was due to PP-1G form of the enzyme. |
| 102 | 7822300 | Insulin stimulated PP-1G (120% over basal levels) without affecting the other forms of PP-1 in the PF. |
| 103 | 7822300 | Insulin activation of PP-1 was accompanied by > 2-fold increase in the phosphorylation state of the 160-kDa regulatory subunit of PP-1. |
| 104 | 7822300 | Stimulation of p21Ras/mitogen-activated protein kinase pathway (MAP) with GTP analogues also resulted in stimulation of PP-1 similar to insulin. |
| 105 | 7822300 | The insulin effect on MAP kinase and PP-1 activation was blocked by a GTP antagonist, guanyl-5'-yl thiophosphate. |
| 106 | 7822300 | The inhibitors of MAP kinase activation (viz. cAMP agonists, SpcAMP and ML-9) also blocked PP-1 stimulation by insulin. |
| 107 | 7822300 | The time course of MAP kinase activation preceded the phosphorylation of PP-1 regulatory subunit and PP-1 activation. |
| 108 | 7822300 | We conclude that insulin rapidly activates a membrane-associated PP-1 in adipocytes, which may be similar to rabbit skeletal muscle PP-1G, and the activation is mediated by p21Ras/MAP kinase pathway. |
| 109 | 7822300 | Stimulation of protein phosphatase-1 activity by insulin in rat adipocytes. |
| 110 | 7822300 | In this study, we examined the distribution of protein serine/threonine phosphatase-1 (PP-1) and analyzed the effect of insulin on PP-1 and its mechanism of activation in freshly isolated rat adipocytes. |
| 111 | 7822300 | The adipocyte particulate fraction (PF) constituted approximately 80% of cellular PP-1 activity, while PP-2A was entirely cytosolic. |
| 112 | 7822300 | Insulin rapidly stimulated PF PP-1 in a time- and dose-dependent manner (maximum stimulation at 5 min with 4 nM insulin). |
| 113 | 7822300 | Immunoprecipitation of PF with an antibody against the site-1 sequence of rabbit skeletal muscle glycogen-associated PP-1 (PP-1G) subunit indicated that approximately 40% of adipocyte PP-1 activity was due to PP-1G form of the enzyme. |
| 114 | 7822300 | Insulin stimulated PP-1G (120% over basal levels) without affecting the other forms of PP-1 in the PF. |
| 115 | 7822300 | Insulin activation of PP-1 was accompanied by > 2-fold increase in the phosphorylation state of the 160-kDa regulatory subunit of PP-1. |
| 116 | 7822300 | Stimulation of p21Ras/mitogen-activated protein kinase pathway (MAP) with GTP analogues also resulted in stimulation of PP-1 similar to insulin. |
| 117 | 7822300 | The insulin effect on MAP kinase and PP-1 activation was blocked by a GTP antagonist, guanyl-5'-yl thiophosphate. |
| 118 | 7822300 | The inhibitors of MAP kinase activation (viz. cAMP agonists, SpcAMP and ML-9) also blocked PP-1 stimulation by insulin. |
| 119 | 7822300 | The time course of MAP kinase activation preceded the phosphorylation of PP-1 regulatory subunit and PP-1 activation. |
| 120 | 7822300 | We conclude that insulin rapidly activates a membrane-associated PP-1 in adipocytes, which may be similar to rabbit skeletal muscle PP-1G, and the activation is mediated by p21Ras/MAP kinase pathway. |
| 121 | 7961833 | Insulin receptor substrate-1 mediates phosphatidylinositol 3'-kinase and p70S6k signaling during insulin, insulin-like growth factor-1, and interleukin-4 stimulation. |
| 122 | 7961833 | Insulin Receptor Substrate-1 (IRS-1) is an endogenous cellular protein that is tyrosine phosphorylated during stimulation of cells with insulin, IGF-1, and interleukin 4 (IL-4). |
| 123 | 7961833 | The 32D myeloid progenitor cell line contains few insulin receptors and no detectable IRS-1. |
| 124 | 7961833 | Expression of the insulin receptor alone partially mediates insulin-stimulated microtubule-associated protein (MAP) kinase activation, and the addition of IRS-1 enhances this effect (Myers, M. |
| 125 | 7961833 | Expression of IRS-1 alone in 32D cells mediates the stimulation of p70S6k by insulin, IGF-1, or IL-4; addition of insulin receptor to these cells increases the sensitivity of the insulin response. |
| 126 | 7961833 | In contrast, full insulin stimulation of PI 3'-kinase requires both the insulin receptor and IRS-1, suggesting that a high level of IRS-1 phosphorylation is required for insulin-stimulated PI 3'-kinase activation, whereas a low level of IRS-1 tyrosine phosphorylation transmits an essential signal to p70S6k. |
| 127 | 7961833 | Both insulin receptors and IRS-1 are required for mitogenic signaling in 32D cells suggesting that MAP kinase or p70S6k alone are not sufficient, and that both or additional unknown IRS-1-mediated signals are necessary. |
| 128 | 7961833 | Insulin receptor substrate-1 mediates phosphatidylinositol 3'-kinase and p70S6k signaling during insulin, insulin-like growth factor-1, and interleukin-4 stimulation. |
| 129 | 7961833 | Insulin Receptor Substrate-1 (IRS-1) is an endogenous cellular protein that is tyrosine phosphorylated during stimulation of cells with insulin, IGF-1, and interleukin 4 (IL-4). |
| 130 | 7961833 | The 32D myeloid progenitor cell line contains few insulin receptors and no detectable IRS-1. |
| 131 | 7961833 | Expression of the insulin receptor alone partially mediates insulin-stimulated microtubule-associated protein (MAP) kinase activation, and the addition of IRS-1 enhances this effect (Myers, M. |
| 132 | 7961833 | Expression of IRS-1 alone in 32D cells mediates the stimulation of p70S6k by insulin, IGF-1, or IL-4; addition of insulin receptor to these cells increases the sensitivity of the insulin response. |
| 133 | 7961833 | In contrast, full insulin stimulation of PI 3'-kinase requires both the insulin receptor and IRS-1, suggesting that a high level of IRS-1 phosphorylation is required for insulin-stimulated PI 3'-kinase activation, whereas a low level of IRS-1 tyrosine phosphorylation transmits an essential signal to p70S6k. |
| 134 | 7961833 | Both insulin receptors and IRS-1 are required for mitogenic signaling in 32D cells suggesting that MAP kinase or p70S6k alone are not sufficient, and that both or additional unknown IRS-1-mediated signals are necessary. |
| 135 | 7997269 | Role of SAPK/ERK kinase-1 in the stress-activated pathway regulating transcription factor c-Jun. |
| 136 | 7997269 | The stress-activated protein kinases (SAPKs), which are distantly related to the MAP kinases, are the dominant c-Jun amino-terminal protein kinases activated in response to a variety of cellular stresses, including treatment with tumour-necrosis factor-alpha and interleukin-beta (refs 1, 2). |
| 137 | 7997269 | SAPK phosphorylation of c-Jun probably activates the c-Jun transactivation function. |
| 138 | 7997269 | SAPKs are part of a signal transduction cascade related to, but distinct from, the MAPK pathway. |
| 139 | 7997269 | We have now identified a novel protein kinase, called SAPK/ERK kinase-1 (SEK1), which is structurally related to the MAP kinase kinases (MEKs). |
| 140 | 7997269 | SEK1 is a potent activator of the SAPKs in vitro and in vivo. |
| 141 | 7997269 | An inactive SEK1 mutant blocks SAPK activation by extracellular stimuli without interfering with the MAPK pathway. |
| 142 | 7997269 | Although alternative mechanisms of SAPK activation may exist, as an immediate upstream activator of the SAPKs, SEK1 further defines a signalling cascade that couples cellular stress agonists to the c-Jun transcription factor. |
| 143 | 8058065 | The level of insulin receptor tyrosine kinase activity modulates the activities of phosphatidylinositol 3-kinase, microtubule-associated protein, and S6 kinases. |
| 144 | 8058065 | The role of insulin receptor tyrosine kinase activity in stimulation of intracellular enzymes linked to insulin action [phosphatidylinositol 3-kinase (PtdIns 3-kinase), microtubule-associated protein (MAP) kinase, and S6 kinases] was studied in Chinese hamster ovary cells which overexpress wild type human insulin receptors, receptors with reduced kinase activity due to substitution of Phe for Tyr1146 (single-Phe), Tyr1150,1151 (double-Phe), and Tyr1146,1150,1151 (triple-Phe), or kinase-inactive receptors with a substitution of Ala for Lys1018 in the ATP binding site (A1018). |
| 145 | 8058065 | Overexpression of the wild type insulin receptor increased both maximal insulin receptor substrate-1-associated and total insulin-stimulated PtdIns 3-kinase activity, as well as S6 and MAP kinase activities 2.0- to 3.6-fold. |
| 146 | 8058065 | Expression of the single- and double-Phe mutant receptors also enhanced maximal PtdIns 3-kinase activity, but had no effect on insulin sensitivity, whereas expression of either the triple-Phe or kinase-inactive receptors did not enhance insulin stimulation or increase insulin sensitivity as compared to the control cells. |
| 147 | 8058065 | When comparing the mutant and wild type receptors, differences in insulin sensitivity were least for insulin-stimulated MAP kinase and greatest for S6 kinase; with the latter there was greater than a 1000-fold difference in insulin sensitivity when cells that overexpress wild type vs. kinase-inactive insulin receptors were compared. |
| 148 | 8058065 | The level of insulin receptor tyrosine kinase activity modulates the activities of phosphatidylinositol 3-kinase, microtubule-associated protein, and S6 kinases. |
| 149 | 8058065 | The role of insulin receptor tyrosine kinase activity in stimulation of intracellular enzymes linked to insulin action [phosphatidylinositol 3-kinase (PtdIns 3-kinase), microtubule-associated protein (MAP) kinase, and S6 kinases] was studied in Chinese hamster ovary cells which overexpress wild type human insulin receptors, receptors with reduced kinase activity due to substitution of Phe for Tyr1146 (single-Phe), Tyr1150,1151 (double-Phe), and Tyr1146,1150,1151 (triple-Phe), or kinase-inactive receptors with a substitution of Ala for Lys1018 in the ATP binding site (A1018). |
| 150 | 8058065 | Overexpression of the wild type insulin receptor increased both maximal insulin receptor substrate-1-associated and total insulin-stimulated PtdIns 3-kinase activity, as well as S6 and MAP kinase activities 2.0- to 3.6-fold. |
| 151 | 8058065 | Expression of the single- and double-Phe mutant receptors also enhanced maximal PtdIns 3-kinase activity, but had no effect on insulin sensitivity, whereas expression of either the triple-Phe or kinase-inactive receptors did not enhance insulin stimulation or increase insulin sensitivity as compared to the control cells. |
| 152 | 8058065 | When comparing the mutant and wild type receptors, differences in insulin sensitivity were least for insulin-stimulated MAP kinase and greatest for S6 kinase; with the latter there was greater than a 1000-fold difference in insulin sensitivity when cells that overexpress wild type vs. kinase-inactive insulin receptors were compared. |
| 153 | 8058065 | The level of insulin receptor tyrosine kinase activity modulates the activities of phosphatidylinositol 3-kinase, microtubule-associated protein, and S6 kinases. |
| 154 | 8058065 | The role of insulin receptor tyrosine kinase activity in stimulation of intracellular enzymes linked to insulin action [phosphatidylinositol 3-kinase (PtdIns 3-kinase), microtubule-associated protein (MAP) kinase, and S6 kinases] was studied in Chinese hamster ovary cells which overexpress wild type human insulin receptors, receptors with reduced kinase activity due to substitution of Phe for Tyr1146 (single-Phe), Tyr1150,1151 (double-Phe), and Tyr1146,1150,1151 (triple-Phe), or kinase-inactive receptors with a substitution of Ala for Lys1018 in the ATP binding site (A1018). |
| 155 | 8058065 | Overexpression of the wild type insulin receptor increased both maximal insulin receptor substrate-1-associated and total insulin-stimulated PtdIns 3-kinase activity, as well as S6 and MAP kinase activities 2.0- to 3.6-fold. |
| 156 | 8058065 | Expression of the single- and double-Phe mutant receptors also enhanced maximal PtdIns 3-kinase activity, but had no effect on insulin sensitivity, whereas expression of either the triple-Phe or kinase-inactive receptors did not enhance insulin stimulation or increase insulin sensitivity as compared to the control cells. |
| 157 | 8058065 | When comparing the mutant and wild type receptors, differences in insulin sensitivity were least for insulin-stimulated MAP kinase and greatest for S6 kinase; with the latter there was greater than a 1000-fold difference in insulin sensitivity when cells that overexpress wild type vs. kinase-inactive insulin receptors were compared. |
| 158 | 8196603 | GRB-2 is a small SH2- and SH3 domain-containing adapter protein that associates with the mammalian SOS homolog to regulate p21ras during growth factor signaling. |
| 159 | 8196603 | During insulin stimulation, GRB-2 binds to the phosphorylated Y895VNI motif of IRS-1. |
| 160 | 8196603 | The myeloid progenitor cell line, 32-D, is insensitive to insulin because it contains few insulin receptors and no IRS-1. |
| 161 | 8196603 | Coexpression of IRS-1 or IRS-1F-895 with the insulin receptor was required for insulin-stimulated mitogenesis in 32-D cells, while expression of the insulin receptor alone was sufficient to mediate insulin-stimulated tyrosine phosphorylation of Shc and activation of p21ras and mitogen-activated protein (MAP) kinase. |
| 162 | 8196603 | The Shc-GRB-2 complex formed during insulin stimulation is a possible mediator of p21ras and MAP kinase activation in IRS-1-deficient 32-D cells. |
| 163 | 8196603 | Interestingly, IRS-1, but not IRS-1F-895, enhanced the stimulation of MAP kinase by insulin in 32-D cells expressing insulin receptors. |
| 164 | 8196603 | Thus, IRS-1 contributes to the stimulation of MAP kinase by insulin, probably through formation of the IRS-1-GRB-2 complex at Tyr-895. |
| 165 | 8196603 | Our results suggest that the Shc-GRB-2 complex and the activation of p21ras-dependent signaling pathways, including MAP kinase, are insufficient for insulin-stimulated mitogenesis and that the essential function(s) of IRS-1 in proliferative signaling is largely unrelated to IRS-1-GRB-2 complex formation. |
| 166 | 8196603 | GRB-2 is a small SH2- and SH3 domain-containing adapter protein that associates with the mammalian SOS homolog to regulate p21ras during growth factor signaling. |
| 167 | 8196603 | During insulin stimulation, GRB-2 binds to the phosphorylated Y895VNI motif of IRS-1. |
| 168 | 8196603 | The myeloid progenitor cell line, 32-D, is insensitive to insulin because it contains few insulin receptors and no IRS-1. |
| 169 | 8196603 | Coexpression of IRS-1 or IRS-1F-895 with the insulin receptor was required for insulin-stimulated mitogenesis in 32-D cells, while expression of the insulin receptor alone was sufficient to mediate insulin-stimulated tyrosine phosphorylation of Shc and activation of p21ras and mitogen-activated protein (MAP) kinase. |
| 170 | 8196603 | The Shc-GRB-2 complex formed during insulin stimulation is a possible mediator of p21ras and MAP kinase activation in IRS-1-deficient 32-D cells. |
| 171 | 8196603 | Interestingly, IRS-1, but not IRS-1F-895, enhanced the stimulation of MAP kinase by insulin in 32-D cells expressing insulin receptors. |
| 172 | 8196603 | Thus, IRS-1 contributes to the stimulation of MAP kinase by insulin, probably through formation of the IRS-1-GRB-2 complex at Tyr-895. |
| 173 | 8196603 | Our results suggest that the Shc-GRB-2 complex and the activation of p21ras-dependent signaling pathways, including MAP kinase, are insufficient for insulin-stimulated mitogenesis and that the essential function(s) of IRS-1 in proliferative signaling is largely unrelated to IRS-1-GRB-2 complex formation. |
| 174 | 8196603 | GRB-2 is a small SH2- and SH3 domain-containing adapter protein that associates with the mammalian SOS homolog to regulate p21ras during growth factor signaling. |
| 175 | 8196603 | During insulin stimulation, GRB-2 binds to the phosphorylated Y895VNI motif of IRS-1. |
| 176 | 8196603 | The myeloid progenitor cell line, 32-D, is insensitive to insulin because it contains few insulin receptors and no IRS-1. |
| 177 | 8196603 | Coexpression of IRS-1 or IRS-1F-895 with the insulin receptor was required for insulin-stimulated mitogenesis in 32-D cells, while expression of the insulin receptor alone was sufficient to mediate insulin-stimulated tyrosine phosphorylation of Shc and activation of p21ras and mitogen-activated protein (MAP) kinase. |
| 178 | 8196603 | The Shc-GRB-2 complex formed during insulin stimulation is a possible mediator of p21ras and MAP kinase activation in IRS-1-deficient 32-D cells. |
| 179 | 8196603 | Interestingly, IRS-1, but not IRS-1F-895, enhanced the stimulation of MAP kinase by insulin in 32-D cells expressing insulin receptors. |
| 180 | 8196603 | Thus, IRS-1 contributes to the stimulation of MAP kinase by insulin, probably through formation of the IRS-1-GRB-2 complex at Tyr-895. |
| 181 | 8196603 | Our results suggest that the Shc-GRB-2 complex and the activation of p21ras-dependent signaling pathways, including MAP kinase, are insufficient for insulin-stimulated mitogenesis and that the essential function(s) of IRS-1 in proliferative signaling is largely unrelated to IRS-1-GRB-2 complex formation. |
| 182 | 8196603 | GRB-2 is a small SH2- and SH3 domain-containing adapter protein that associates with the mammalian SOS homolog to regulate p21ras during growth factor signaling. |
| 183 | 8196603 | During insulin stimulation, GRB-2 binds to the phosphorylated Y895VNI motif of IRS-1. |
| 184 | 8196603 | The myeloid progenitor cell line, 32-D, is insensitive to insulin because it contains few insulin receptors and no IRS-1. |
| 185 | 8196603 | Coexpression of IRS-1 or IRS-1F-895 with the insulin receptor was required for insulin-stimulated mitogenesis in 32-D cells, while expression of the insulin receptor alone was sufficient to mediate insulin-stimulated tyrosine phosphorylation of Shc and activation of p21ras and mitogen-activated protein (MAP) kinase. |
| 186 | 8196603 | The Shc-GRB-2 complex formed during insulin stimulation is a possible mediator of p21ras and MAP kinase activation in IRS-1-deficient 32-D cells. |
| 187 | 8196603 | Interestingly, IRS-1, but not IRS-1F-895, enhanced the stimulation of MAP kinase by insulin in 32-D cells expressing insulin receptors. |
| 188 | 8196603 | Thus, IRS-1 contributes to the stimulation of MAP kinase by insulin, probably through formation of the IRS-1-GRB-2 complex at Tyr-895. |
| 189 | 8196603 | Our results suggest that the Shc-GRB-2 complex and the activation of p21ras-dependent signaling pathways, including MAP kinase, are insufficient for insulin-stimulated mitogenesis and that the essential function(s) of IRS-1 in proliferative signaling is largely unrelated to IRS-1-GRB-2 complex formation. |
| 190 | 8196603 | GRB-2 is a small SH2- and SH3 domain-containing adapter protein that associates with the mammalian SOS homolog to regulate p21ras during growth factor signaling. |
| 191 | 8196603 | During insulin stimulation, GRB-2 binds to the phosphorylated Y895VNI motif of IRS-1. |
| 192 | 8196603 | The myeloid progenitor cell line, 32-D, is insensitive to insulin because it contains few insulin receptors and no IRS-1. |
| 193 | 8196603 | Coexpression of IRS-1 or IRS-1F-895 with the insulin receptor was required for insulin-stimulated mitogenesis in 32-D cells, while expression of the insulin receptor alone was sufficient to mediate insulin-stimulated tyrosine phosphorylation of Shc and activation of p21ras and mitogen-activated protein (MAP) kinase. |
| 194 | 8196603 | The Shc-GRB-2 complex formed during insulin stimulation is a possible mediator of p21ras and MAP kinase activation in IRS-1-deficient 32-D cells. |
| 195 | 8196603 | Interestingly, IRS-1, but not IRS-1F-895, enhanced the stimulation of MAP kinase by insulin in 32-D cells expressing insulin receptors. |
| 196 | 8196603 | Thus, IRS-1 contributes to the stimulation of MAP kinase by insulin, probably through formation of the IRS-1-GRB-2 complex at Tyr-895. |
| 197 | 8196603 | Our results suggest that the Shc-GRB-2 complex and the activation of p21ras-dependent signaling pathways, including MAP kinase, are insufficient for insulin-stimulated mitogenesis and that the essential function(s) of IRS-1 in proliferative signaling is largely unrelated to IRS-1-GRB-2 complex formation. |
| 198 | 8393870 | In CHO-Y960F cells, tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), the activation of phosphatidylinositol 3-kinase in the anti-phosphotyrosine and anti-IRS-1 immunoprecipitates, the activation of mitogen-activated protein (MAP) kinase, and biological actions were also impaired. |
| 199 | 8393870 | In addition, although the deletion of residues 954-965 severely impaired insulin internalization, the deletion of NPXY (957-960), the internalization signal of the low density lipoprotein receptor, did not affect internalization. |
| 200 | 8393870 | These data suggest that: 1) Tyr960 is important for the recognition of pp185/IRS-1, the association of phosphatidylinositol 3-kinase with pp185/IRS-1, and the activation of MAP kinase; 2) MAP kinase may lie downstream of pp185/IRS-1 in insulin's signal transduction; and 3) the juxtamembrane domain, but not NPXY or individual tyrosines, is important for insulin internalization. |
| 201 | 8393870 | In CHO-Y960F cells, tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), the activation of phosphatidylinositol 3-kinase in the anti-phosphotyrosine and anti-IRS-1 immunoprecipitates, the activation of mitogen-activated protein (MAP) kinase, and biological actions were also impaired. |
| 202 | 8393870 | In addition, although the deletion of residues 954-965 severely impaired insulin internalization, the deletion of NPXY (957-960), the internalization signal of the low density lipoprotein receptor, did not affect internalization. |
| 203 | 8393870 | These data suggest that: 1) Tyr960 is important for the recognition of pp185/IRS-1, the association of phosphatidylinositol 3-kinase with pp185/IRS-1, and the activation of MAP kinase; 2) MAP kinase may lie downstream of pp185/IRS-1 in insulin's signal transduction; and 3) the juxtamembrane domain, but not NPXY or individual tyrosines, is important for insulin internalization. |
| 204 | 8529805 | In addition, the finding that the mitogen-activated protein kinase (MAP kinase) pathway was tyrosine phosphorylated, and presumably activated, in endothelial cells after an increase in [Ca2+]i has wideranging implications for these cells. |
| 205 | 8529805 | Indeed, MAP kinase recognizes many different substrates in the cell, including growth factor receptors, microtubule-associated proteins, specific serine-threonine protein kinases, phospholipase A2, and transcription factors. |
| 206 | 8529805 | Indeed, this mediator, which seems to be an endothelium-derived, cytochrome P450-derived metabolite of arachidonic acid, would now appear to represent a substantial constitutive component of the vasodilator response to bradykinin. |
| 207 | 8529805 | In addition, the finding that the mitogen-activated protein kinase (MAP kinase) pathway was tyrosine phosphorylated, and presumably activated, in endothelial cells after an increase in [Ca2+]i has wideranging implications for these cells. |
| 208 | 8529805 | Indeed, MAP kinase recognizes many different substrates in the cell, including growth factor receptors, microtubule-associated proteins, specific serine-threonine protein kinases, phospholipase A2, and transcription factors. |
| 209 | 8529805 | Indeed, this mediator, which seems to be an endothelium-derived, cytochrome P450-derived metabolite of arachidonic acid, would now appear to represent a substantial constitutive component of the vasodilator response to bradykinin. |
| 210 | 8573738 | Abnormalities in protein kinase C and MAP kinase cascade in mesangial cells cultured under high glucose conditions. |
| 211 | 8573738 | In order to clarify the mechanism of mesangial cell dysfunction in diabetes, we examined the activities of protein kinase C (PKC) and mitogen-activated protein kinase (MAPK), important kinases in various cellular functions, and also evaluated the isoenzymes of PKC in mesangial cells cultured under high glucose conditions. |
| 212 | 8573738 | These results indicate that the translocation of PKC alpha and zeta and the activation of MAPK under high glucose conditions might be underlying mechanisms of the functional disturbance of mesangial cells in diabetes. |
| 213 | 8621547 | The linkage between Gialpha2 and morphogen-induced promotion of F9 embryonic teratocarcinoma stem (F9 stem) cells to primitive endoderm was explored using probes of the mitogen-activated protein (MAP) kinase network. |
| 214 | 8621547 | The morphogen-induced decline in Gialpha2 is shown to trigger activation of phospholipase C, thereby activating protein kinase C, MAP kinase, and cell progression to primitive endoderm. |
| 215 | 8621547 | In the absence of retinoic acid, reduction-of-function mutants (Gialpha2-deficient) display the effects of morphogen, i.e. activation of phospholipase C, protein kinase C, MAP kinase, and progression to primitive endoderm. |
| 216 | 8621547 | Gain-of-function mutants (expressing the Q205L activating-mutation of Gialpha2) displayed no activation of phospholipase C, protein kinase C, MAP kinase and no progression to primitive endoderm, even in the presence of retinoic acid. |
| 217 | 8621547 | Morphogen triggers F9 stem cell progression by triggering Gialpha2 loss and thereby activation of downstream elements, including protein kinase C and MAP kinase. |
| 218 | 8621547 | The linkage between Gialpha2 and morphogen-induced promotion of F9 embryonic teratocarcinoma stem (F9 stem) cells to primitive endoderm was explored using probes of the mitogen-activated protein (MAP) kinase network. |
| 219 | 8621547 | The morphogen-induced decline in Gialpha2 is shown to trigger activation of phospholipase C, thereby activating protein kinase C, MAP kinase, and cell progression to primitive endoderm. |
| 220 | 8621547 | In the absence of retinoic acid, reduction-of-function mutants (Gialpha2-deficient) display the effects of morphogen, i.e. activation of phospholipase C, protein kinase C, MAP kinase, and progression to primitive endoderm. |
| 221 | 8621547 | Gain-of-function mutants (expressing the Q205L activating-mutation of Gialpha2) displayed no activation of phospholipase C, protein kinase C, MAP kinase and no progression to primitive endoderm, even in the presence of retinoic acid. |
| 222 | 8621547 | Morphogen triggers F9 stem cell progression by triggering Gialpha2 loss and thereby activation of downstream elements, including protein kinase C and MAP kinase. |
| 223 | 8621547 | The linkage between Gialpha2 and morphogen-induced promotion of F9 embryonic teratocarcinoma stem (F9 stem) cells to primitive endoderm was explored using probes of the mitogen-activated protein (MAP) kinase network. |
| 224 | 8621547 | The morphogen-induced decline in Gialpha2 is shown to trigger activation of phospholipase C, thereby activating protein kinase C, MAP kinase, and cell progression to primitive endoderm. |
| 225 | 8621547 | In the absence of retinoic acid, reduction-of-function mutants (Gialpha2-deficient) display the effects of morphogen, i.e. activation of phospholipase C, protein kinase C, MAP kinase, and progression to primitive endoderm. |
| 226 | 8621547 | Gain-of-function mutants (expressing the Q205L activating-mutation of Gialpha2) displayed no activation of phospholipase C, protein kinase C, MAP kinase and no progression to primitive endoderm, even in the presence of retinoic acid. |
| 227 | 8621547 | Morphogen triggers F9 stem cell progression by triggering Gialpha2 loss and thereby activation of downstream elements, including protein kinase C and MAP kinase. |
| 228 | 8621547 | The linkage between Gialpha2 and morphogen-induced promotion of F9 embryonic teratocarcinoma stem (F9 stem) cells to primitive endoderm was explored using probes of the mitogen-activated protein (MAP) kinase network. |
| 229 | 8621547 | The morphogen-induced decline in Gialpha2 is shown to trigger activation of phospholipase C, thereby activating protein kinase C, MAP kinase, and cell progression to primitive endoderm. |
| 230 | 8621547 | In the absence of retinoic acid, reduction-of-function mutants (Gialpha2-deficient) display the effects of morphogen, i.e. activation of phospholipase C, protein kinase C, MAP kinase, and progression to primitive endoderm. |
| 231 | 8621547 | Gain-of-function mutants (expressing the Q205L activating-mutation of Gialpha2) displayed no activation of phospholipase C, protein kinase C, MAP kinase and no progression to primitive endoderm, even in the presence of retinoic acid. |
| 232 | 8621547 | Morphogen triggers F9 stem cell progression by triggering Gialpha2 loss and thereby activation of downstream elements, including protein kinase C and MAP kinase. |
| 233 | 8621547 | The linkage between Gialpha2 and morphogen-induced promotion of F9 embryonic teratocarcinoma stem (F9 stem) cells to primitive endoderm was explored using probes of the mitogen-activated protein (MAP) kinase network. |
| 234 | 8621547 | The morphogen-induced decline in Gialpha2 is shown to trigger activation of phospholipase C, thereby activating protein kinase C, MAP kinase, and cell progression to primitive endoderm. |
| 235 | 8621547 | In the absence of retinoic acid, reduction-of-function mutants (Gialpha2-deficient) display the effects of morphogen, i.e. activation of phospholipase C, protein kinase C, MAP kinase, and progression to primitive endoderm. |
| 236 | 8621547 | Gain-of-function mutants (expressing the Q205L activating-mutation of Gialpha2) displayed no activation of phospholipase C, protein kinase C, MAP kinase and no progression to primitive endoderm, even in the presence of retinoic acid. |
| 237 | 8621547 | Morphogen triggers F9 stem cell progression by triggering Gialpha2 loss and thereby activation of downstream elements, including protein kinase C and MAP kinase. |
| 238 | 8644999 | Addition of zinc chloride to bombesin-sensitive Swiss 3T3 mouse fibroblasts induced a fourfold stimulation in the cytosolic myelin basic protein kinase activity. |
| 239 | 8644999 | The kinase activity coeluted with p42 MAP kinase using chromatography on Mono-Q ion exchange. |
| 240 | 8644999 | Immunoprecipitation against the p85 subunit of phosphatidylinositol 3-kinase resulted in the appearance of two phosphotyrosine-containing proteins, 100 and 115 kDa, in extracts from cells treated with zinc or epidermal growth factor, indicating that the tyrosine phosphorylation was recognized by the corresponding SH2-domains. |
| 241 | 8644999 | The present study demonstrates that extracellular zinc has the potential to partially mimic the action of growth factors on intracellular MAP kinase activation and protein tyrosine phosphorylation. |
| 242 | 8644999 | Addition of zinc chloride to bombesin-sensitive Swiss 3T3 mouse fibroblasts induced a fourfold stimulation in the cytosolic myelin basic protein kinase activity. |
| 243 | 8644999 | The kinase activity coeluted with p42 MAP kinase using chromatography on Mono-Q ion exchange. |
| 244 | 8644999 | Immunoprecipitation against the p85 subunit of phosphatidylinositol 3-kinase resulted in the appearance of two phosphotyrosine-containing proteins, 100 and 115 kDa, in extracts from cells treated with zinc or epidermal growth factor, indicating that the tyrosine phosphorylation was recognized by the corresponding SH2-domains. |
| 245 | 8644999 | The present study demonstrates that extracellular zinc has the potential to partially mimic the action of growth factors on intracellular MAP kinase activation and protein tyrosine phosphorylation. |
| 246 | 8770036 | Studies in mammalian cells have established the existence of at least three distinct mitogen-activated protein kinase (MAP kinase) signaling pathways that are activated by a variety of growth factors and/or environmental stressors. |
| 247 | 8770036 | We determined whether physical exercise, a physiological stressor, and insulin, a metabolic stimulator and growth factor, activate the c-jun NH2-terminus kinase (JNK), the p38 kinase, and/or the extracellular regulatory kinases (ERK; p42MAPK and p44MAPK) signaling pathways in rat skeletal muscle. |
| 248 | 8770036 | Exercise increased skeletal muscle JNK activity by two- to threefold throughout the time course studied, whereas insulin did not significantly increase JNK activity. |
| 249 | 8770036 | Activation of these MAP kinase signaling pathways may mediate changes in skeletal muscle growth and metabolism that occur in response to exercise. |
| 250 | 8770036 | Studies in mammalian cells have established the existence of at least three distinct mitogen-activated protein kinase (MAP kinase) signaling pathways that are activated by a variety of growth factors and/or environmental stressors. |
| 251 | 8770036 | We determined whether physical exercise, a physiological stressor, and insulin, a metabolic stimulator and growth factor, activate the c-jun NH2-terminus kinase (JNK), the p38 kinase, and/or the extracellular regulatory kinases (ERK; p42MAPK and p44MAPK) signaling pathways in rat skeletal muscle. |
| 252 | 8770036 | Exercise increased skeletal muscle JNK activity by two- to threefold throughout the time course studied, whereas insulin did not significantly increase JNK activity. |
| 253 | 8770036 | Activation of these MAP kinase signaling pathways may mediate changes in skeletal muscle growth and metabolism that occur in response to exercise. |
| 254 | 8803477 | To further delineate the TNF-alpha signal transduction pathway mediating glucose metabolism, we utilized L6 rat myoblasts which contain the receptors for the insulin-like growth factor-I (IGF-I) and TNF-alpha, and the ability of both ligands to stimulate glucose uptake was compared. |
| 255 | 8803477 | IGF-I (6.5 nM) maximally stimulated glucose uptake 7-fold after 24 h incubation, while 23 nM TNF-alpha maximally stimulated glucose uptake 3-fold only after 48 h incubation. |
| 256 | 8803477 | IGF-I receptor beta-subunit, insulin receptor substrate-1 (IRS-1), and mitogen-activated protein (MAP) kinase were all phosphorylated in response to 6.5 nM IGF-I after 10 min incubation. |
| 257 | 8803477 | In contrast, the treatment with 23 nM TNF-alpha failed to phosphorylate either IGF-I receptor beta-subunit or IRS-1 but did phosphorylate MAP kinase as much as IGF-I did. |
| 258 | 8803477 | Despite a similar extent to which TNF-alpha induced MAP kinase phosphorylation as IGF-I did, TNF-alpha stimulated glucose uptake less compared to IGF-I. |
| 259 | 8803477 | The results indicate that MAP kinase phosphorylation is not sufficient for glucose uptake in L6 myoblasts. |
| 260 | 8803477 | TNF-alpha-elicited signal transduction to glucose uptake may utilize a different pathway from that seen with IGF-I. |
| 261 | 8803477 | To further delineate the TNF-alpha signal transduction pathway mediating glucose metabolism, we utilized L6 rat myoblasts which contain the receptors for the insulin-like growth factor-I (IGF-I) and TNF-alpha, and the ability of both ligands to stimulate glucose uptake was compared. |
| 262 | 8803477 | IGF-I (6.5 nM) maximally stimulated glucose uptake 7-fold after 24 h incubation, while 23 nM TNF-alpha maximally stimulated glucose uptake 3-fold only after 48 h incubation. |
| 263 | 8803477 | IGF-I receptor beta-subunit, insulin receptor substrate-1 (IRS-1), and mitogen-activated protein (MAP) kinase were all phosphorylated in response to 6.5 nM IGF-I after 10 min incubation. |
| 264 | 8803477 | In contrast, the treatment with 23 nM TNF-alpha failed to phosphorylate either IGF-I receptor beta-subunit or IRS-1 but did phosphorylate MAP kinase as much as IGF-I did. |
| 265 | 8803477 | Despite a similar extent to which TNF-alpha induced MAP kinase phosphorylation as IGF-I did, TNF-alpha stimulated glucose uptake less compared to IGF-I. |
| 266 | 8803477 | The results indicate that MAP kinase phosphorylation is not sufficient for glucose uptake in L6 myoblasts. |
| 267 | 8803477 | TNF-alpha-elicited signal transduction to glucose uptake may utilize a different pathway from that seen with IGF-I. |
| 268 | 8803477 | To further delineate the TNF-alpha signal transduction pathway mediating glucose metabolism, we utilized L6 rat myoblasts which contain the receptors for the insulin-like growth factor-I (IGF-I) and TNF-alpha, and the ability of both ligands to stimulate glucose uptake was compared. |
| 269 | 8803477 | IGF-I (6.5 nM) maximally stimulated glucose uptake 7-fold after 24 h incubation, while 23 nM TNF-alpha maximally stimulated glucose uptake 3-fold only after 48 h incubation. |
| 270 | 8803477 | IGF-I receptor beta-subunit, insulin receptor substrate-1 (IRS-1), and mitogen-activated protein (MAP) kinase were all phosphorylated in response to 6.5 nM IGF-I after 10 min incubation. |
| 271 | 8803477 | In contrast, the treatment with 23 nM TNF-alpha failed to phosphorylate either IGF-I receptor beta-subunit or IRS-1 but did phosphorylate MAP kinase as much as IGF-I did. |
| 272 | 8803477 | Despite a similar extent to which TNF-alpha induced MAP kinase phosphorylation as IGF-I did, TNF-alpha stimulated glucose uptake less compared to IGF-I. |
| 273 | 8803477 | The results indicate that MAP kinase phosphorylation is not sufficient for glucose uptake in L6 myoblasts. |
| 274 | 8803477 | TNF-alpha-elicited signal transduction to glucose uptake may utilize a different pathway from that seen with IGF-I. |
| 275 | 8803477 | To further delineate the TNF-alpha signal transduction pathway mediating glucose metabolism, we utilized L6 rat myoblasts which contain the receptors for the insulin-like growth factor-I (IGF-I) and TNF-alpha, and the ability of both ligands to stimulate glucose uptake was compared. |
| 276 | 8803477 | IGF-I (6.5 nM) maximally stimulated glucose uptake 7-fold after 24 h incubation, while 23 nM TNF-alpha maximally stimulated glucose uptake 3-fold only after 48 h incubation. |
| 277 | 8803477 | IGF-I receptor beta-subunit, insulin receptor substrate-1 (IRS-1), and mitogen-activated protein (MAP) kinase were all phosphorylated in response to 6.5 nM IGF-I after 10 min incubation. |
| 278 | 8803477 | In contrast, the treatment with 23 nM TNF-alpha failed to phosphorylate either IGF-I receptor beta-subunit or IRS-1 but did phosphorylate MAP kinase as much as IGF-I did. |
| 279 | 8803477 | Despite a similar extent to which TNF-alpha induced MAP kinase phosphorylation as IGF-I did, TNF-alpha stimulated glucose uptake less compared to IGF-I. |
| 280 | 8803477 | The results indicate that MAP kinase phosphorylation is not sufficient for glucose uptake in L6 myoblasts. |
| 281 | 8803477 | TNF-alpha-elicited signal transduction to glucose uptake may utilize a different pathway from that seen with IGF-I. |
| 282 | 8897827 | Mechanisms of ANG II-induced mitogenic responses: role of 12-lipoxygenase and biphasic MAP kinase. |
| 283 | 8897827 | ANG II treatment also induced a biphasic elevation of mitogen-activated protein (MAP) kinase activity of both p42MAPK and p44MAPK with a rapid early peak at 5 min (2- to 6-fold) followed by a second sustained increase that reached a peak at 3 h (1.5- to 3-fold). |
| 284 | 8897827 | We have previously shown that the 12-lipoxygenase (12-LO) pathway of arachidonate metabolism plays a key role in ANG II-induced growth of vascular smooth muscle and adrenal cells. |
| 285 | 8897827 | CDC and PTX also selectively blocked only the late (3 h) peak of ANG II-induced MAP kinase activity, suggesting that the late sustained peak of MAP kinase activity may be linked to the mitogenic effect of ANG II. |
| 286 | 8897827 | Direct addition of 12-HETE (10(-7) M) led to a sustained increase in cell number similar to the effect of ANG II. 12-HETE also caused an increase in MAP kinase activity, and 12-HETE effects were blocked by PTX. |
| 287 | 8897827 | These results suggest that ANG II-induced mitogenic response is associated with sustained MAP kinase activation and that LO activation may play a key role in this process. |
| 288 | 8897827 | Mechanisms of ANG II-induced mitogenic responses: role of 12-lipoxygenase and biphasic MAP kinase. |
| 289 | 8897827 | ANG II treatment also induced a biphasic elevation of mitogen-activated protein (MAP) kinase activity of both p42MAPK and p44MAPK with a rapid early peak at 5 min (2- to 6-fold) followed by a second sustained increase that reached a peak at 3 h (1.5- to 3-fold). |
| 290 | 8897827 | We have previously shown that the 12-lipoxygenase (12-LO) pathway of arachidonate metabolism plays a key role in ANG II-induced growth of vascular smooth muscle and adrenal cells. |
| 291 | 8897827 | CDC and PTX also selectively blocked only the late (3 h) peak of ANG II-induced MAP kinase activity, suggesting that the late sustained peak of MAP kinase activity may be linked to the mitogenic effect of ANG II. |
| 292 | 8897827 | Direct addition of 12-HETE (10(-7) M) led to a sustained increase in cell number similar to the effect of ANG II. 12-HETE also caused an increase in MAP kinase activity, and 12-HETE effects were blocked by PTX. |
| 293 | 8897827 | These results suggest that ANG II-induced mitogenic response is associated with sustained MAP kinase activation and that LO activation may play a key role in this process. |
| 294 | 8897827 | Mechanisms of ANG II-induced mitogenic responses: role of 12-lipoxygenase and biphasic MAP kinase. |
| 295 | 8897827 | ANG II treatment also induced a biphasic elevation of mitogen-activated protein (MAP) kinase activity of both p42MAPK and p44MAPK with a rapid early peak at 5 min (2- to 6-fold) followed by a second sustained increase that reached a peak at 3 h (1.5- to 3-fold). |
| 296 | 8897827 | We have previously shown that the 12-lipoxygenase (12-LO) pathway of arachidonate metabolism plays a key role in ANG II-induced growth of vascular smooth muscle and adrenal cells. |
| 297 | 8897827 | CDC and PTX also selectively blocked only the late (3 h) peak of ANG II-induced MAP kinase activity, suggesting that the late sustained peak of MAP kinase activity may be linked to the mitogenic effect of ANG II. |
| 298 | 8897827 | Direct addition of 12-HETE (10(-7) M) led to a sustained increase in cell number similar to the effect of ANG II. 12-HETE also caused an increase in MAP kinase activity, and 12-HETE effects were blocked by PTX. |
| 299 | 8897827 | These results suggest that ANG II-induced mitogenic response is associated with sustained MAP kinase activation and that LO activation may play a key role in this process. |
| 300 | 8897827 | Mechanisms of ANG II-induced mitogenic responses: role of 12-lipoxygenase and biphasic MAP kinase. |
| 301 | 8897827 | ANG II treatment also induced a biphasic elevation of mitogen-activated protein (MAP) kinase activity of both p42MAPK and p44MAPK with a rapid early peak at 5 min (2- to 6-fold) followed by a second sustained increase that reached a peak at 3 h (1.5- to 3-fold). |
| 302 | 8897827 | We have previously shown that the 12-lipoxygenase (12-LO) pathway of arachidonate metabolism plays a key role in ANG II-induced growth of vascular smooth muscle and adrenal cells. |
| 303 | 8897827 | CDC and PTX also selectively blocked only the late (3 h) peak of ANG II-induced MAP kinase activity, suggesting that the late sustained peak of MAP kinase activity may be linked to the mitogenic effect of ANG II. |
| 304 | 8897827 | Direct addition of 12-HETE (10(-7) M) led to a sustained increase in cell number similar to the effect of ANG II. 12-HETE also caused an increase in MAP kinase activity, and 12-HETE effects were blocked by PTX. |
| 305 | 8897827 | These results suggest that ANG II-induced mitogenic response is associated with sustained MAP kinase activation and that LO activation may play a key role in this process. |
| 306 | 8897827 | Mechanisms of ANG II-induced mitogenic responses: role of 12-lipoxygenase and biphasic MAP kinase. |
| 307 | 8897827 | ANG II treatment also induced a biphasic elevation of mitogen-activated protein (MAP) kinase activity of both p42MAPK and p44MAPK with a rapid early peak at 5 min (2- to 6-fold) followed by a second sustained increase that reached a peak at 3 h (1.5- to 3-fold). |
| 308 | 8897827 | We have previously shown that the 12-lipoxygenase (12-LO) pathway of arachidonate metabolism plays a key role in ANG II-induced growth of vascular smooth muscle and adrenal cells. |
| 309 | 8897827 | CDC and PTX also selectively blocked only the late (3 h) peak of ANG II-induced MAP kinase activity, suggesting that the late sustained peak of MAP kinase activity may be linked to the mitogenic effect of ANG II. |
| 310 | 8897827 | Direct addition of 12-HETE (10(-7) M) led to a sustained increase in cell number similar to the effect of ANG II. 12-HETE also caused an increase in MAP kinase activity, and 12-HETE effects were blocked by PTX. |
| 311 | 8897827 | These results suggest that ANG II-induced mitogenic response is associated with sustained MAP kinase activation and that LO activation may play a key role in this process. |
| 312 | 8972717 | The serine/threonine phosphatase inhibitor, okadaic acid (OA), exerted several insulin-like effects in rat adipose cells and was, in part, synergistic with insulin. |
| 313 | 8972717 | OA stimulated glucose transport activity, altered the electrophoretic mobility of IRS-1, increased the phosphorylation of the MAP-kinases ERK 1 and 2 on tyrosine sites, markedly increased MAP kinase activity and also acted synergistically with insulin in activating these enzymes. |
| 314 | 8972717 | Staurosporine virtually completely inhibited the insulin-stimulated glucose transport and MAP kinase activation in spite of a maintained high PI 3-kinase activity. |
| 315 | 8972717 | The serine/threonine phosphatase inhibitor, okadaic acid (OA), exerted several insulin-like effects in rat adipose cells and was, in part, synergistic with insulin. |
| 316 | 8972717 | OA stimulated glucose transport activity, altered the electrophoretic mobility of IRS-1, increased the phosphorylation of the MAP-kinases ERK 1 and 2 on tyrosine sites, markedly increased MAP kinase activity and also acted synergistically with insulin in activating these enzymes. |
| 317 | 8972717 | Staurosporine virtually completely inhibited the insulin-stimulated glucose transport and MAP kinase activation in spite of a maintained high PI 3-kinase activity. |
| 318 | 9003010 | Roles of insulin receptor substrate-1 and Shc on insulin-like growth factor I receptor signaling in early passages of cultured human fibroblasts. |
| 319 | 9003010 | Insulin-like growth factor-I (IGF-I) improves glucose metabolism and growth in patients with leprechaunism. |
| 320 | 9003010 | We investigated signal transduction through IGF-I receptor in comparison with epidermal growth factor (EGF) receptor in early passages of cultured skin fibroblasts from a normal subject and a patient with leprechaunism whose insulin receptor tyrosine kinase was almost nonexistent. |
| 321 | 9003010 | Insulin receptor substrate-1 (IRS-1) became tyrosine-phosphorylated and bound growth factor receptor-bound protein 2 (GRB2) quickly by IGF-I. |
| 322 | 9003010 | The association of Shc with GRB2 by IGF-I was detected by immunoblot with anti-Shc antibody but was hardly visible with antiphosphotyrosine antibody, which was in marked contrast to efficient tyrosine phosphorylation of Shc by EGF. |
| 323 | 9003010 | However, the potency of IGF-I for DNA synthesis was far stronger than EGF, which was not parallel with the potency of these growth factors to activate Shc or MAP kinase. |
| 324 | 9003010 | Rather, phosphatidylinositol (PI) 3-kinase activity, which was activated by IGF-I about 5- to 10-fold more strongly than EGF, appeared to correlate with mitogenesis. |
| 325 | 9003010 | Signal transduction pathways following IGF-I receptor or EGF receptor activation were indistinguishable between the normal subject and the patient. |
| 326 | 9003010 | Our results strongly suggest that in human skin fibroblasts, which represent a more physiological cell culture: 1) IRS-1, rather than Shc, is the major tyrosine-phosphorylated protein binding GRB2 in initial phase of IGF-I signaling; 2) mitogenic potency of receptor tyrosine kinases such as IGF-I receptor and EGF receptor may not be determined solely by the amount of Shc-GRB2 complex or the activity of MAP kinase; and 3) in contrast to previous reports, IGF-I and EGF receptor signalings are not defective in leprechaunism. |
| 327 | 9003010 | Roles of insulin receptor substrate-1 and Shc on insulin-like growth factor I receptor signaling in early passages of cultured human fibroblasts. |
| 328 | 9003010 | Insulin-like growth factor-I (IGF-I) improves glucose metabolism and growth in patients with leprechaunism. |
| 329 | 9003010 | We investigated signal transduction through IGF-I receptor in comparison with epidermal growth factor (EGF) receptor in early passages of cultured skin fibroblasts from a normal subject and a patient with leprechaunism whose insulin receptor tyrosine kinase was almost nonexistent. |
| 330 | 9003010 | Insulin receptor substrate-1 (IRS-1) became tyrosine-phosphorylated and bound growth factor receptor-bound protein 2 (GRB2) quickly by IGF-I. |
| 331 | 9003010 | The association of Shc with GRB2 by IGF-I was detected by immunoblot with anti-Shc antibody but was hardly visible with antiphosphotyrosine antibody, which was in marked contrast to efficient tyrosine phosphorylation of Shc by EGF. |
| 332 | 9003010 | However, the potency of IGF-I for DNA synthesis was far stronger than EGF, which was not parallel with the potency of these growth factors to activate Shc or MAP kinase. |
| 333 | 9003010 | Rather, phosphatidylinositol (PI) 3-kinase activity, which was activated by IGF-I about 5- to 10-fold more strongly than EGF, appeared to correlate with mitogenesis. |
| 334 | 9003010 | Signal transduction pathways following IGF-I receptor or EGF receptor activation were indistinguishable between the normal subject and the patient. |
| 335 | 9003010 | Our results strongly suggest that in human skin fibroblasts, which represent a more physiological cell culture: 1) IRS-1, rather than Shc, is the major tyrosine-phosphorylated protein binding GRB2 in initial phase of IGF-I signaling; 2) mitogenic potency of receptor tyrosine kinases such as IGF-I receptor and EGF receptor may not be determined solely by the amount of Shc-GRB2 complex or the activity of MAP kinase; and 3) in contrast to previous reports, IGF-I and EGF receptor signalings are not defective in leprechaunism. |
| 336 | 9133538 | Differential activation of mitogen-activated protein kinase by insulin and epidermal growth factor in 3T3-L1 adipocytes: a possible involvement of PI3-kinase in the activation of the MAP kinase by insulin. |
| 337 | 9133538 | Mitogen-activated protein (MAP) kinase plays crucial roles in cell growth and differentiation. |
| 338 | 9133538 | It has recently been shown that the MAP kinase cascade in growth factor signaling diverges and cross-talks with other signaling pathways. |
| 339 | 9133538 | In the present study, we examined the effects of wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3-kinase), on the activation of Ras, Raf-1 kinase, and MAP kinase by insulin and epidermal growth factor (EGF). |
| 340 | 9133538 | The effect of LY294002, a structurally distinct PI3-kinase inhibitor, on the activation of Raf-1 kinase by both ligands was also examined. |
| 341 | 9133538 | In 3T3-L1 adipocytes, 25 nmol/l wortmannin inhibited the insulin-induced activation of Raf-1 kinase to the basal level, whereas the same dose of wortmannin had little effect on the EGF-induced activation of Raf-1 kinase. |
| 342 | 9133538 | One hundred micromol/l LY294002 blocked insulin-induced activation of Raf-1 kinase without affecting EGF-induced activation of this kinase. |
| 343 | 9133538 | Twenty-five nmol/l wortmannin inhibited the insulin-induced activation of MAP kinase to the basal level with no effect on the EGF-induced activation of this kinase. |
| 344 | 9133538 | In contrast, in Chinese hamster ovary cells overexpressing the human insulin receptor (CHO-HIR cells), neither wortmannin nor LY294002 inhibited the insulin-induced activation of Raf-1 kinase, and wortmannin had little effect on the activation of MAP kinase by insulin. |
| 345 | 9133538 | These results indicate that 1) PI3-kinase or wortmannin-sensitive molecules are involved in the interaction between activated Ras and Raf-1 kinase in the insulin signaling in 3T3-L1 adipocytes, 2) the involvement of PI3-kinase or wortmannin-sensitive molecules in the insulin-induced activation of MAP kinase appears to be cell-type specific, and 3) differential mechanisms to activate Raf-1 kinase and MAP kinase by insulin and EGF exist. |
| 346 | 9133538 | Differential activation of mitogen-activated protein kinase by insulin and epidermal growth factor in 3T3-L1 adipocytes: a possible involvement of PI3-kinase in the activation of the MAP kinase by insulin. |
| 347 | 9133538 | Mitogen-activated protein (MAP) kinase plays crucial roles in cell growth and differentiation. |
| 348 | 9133538 | It has recently been shown that the MAP kinase cascade in growth factor signaling diverges and cross-talks with other signaling pathways. |
| 349 | 9133538 | In the present study, we examined the effects of wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3-kinase), on the activation of Ras, Raf-1 kinase, and MAP kinase by insulin and epidermal growth factor (EGF). |
| 350 | 9133538 | The effect of LY294002, a structurally distinct PI3-kinase inhibitor, on the activation of Raf-1 kinase by both ligands was also examined. |
| 351 | 9133538 | In 3T3-L1 adipocytes, 25 nmol/l wortmannin inhibited the insulin-induced activation of Raf-1 kinase to the basal level, whereas the same dose of wortmannin had little effect on the EGF-induced activation of Raf-1 kinase. |
| 352 | 9133538 | One hundred micromol/l LY294002 blocked insulin-induced activation of Raf-1 kinase without affecting EGF-induced activation of this kinase. |
| 353 | 9133538 | Twenty-five nmol/l wortmannin inhibited the insulin-induced activation of MAP kinase to the basal level with no effect on the EGF-induced activation of this kinase. |
| 354 | 9133538 | In contrast, in Chinese hamster ovary cells overexpressing the human insulin receptor (CHO-HIR cells), neither wortmannin nor LY294002 inhibited the insulin-induced activation of Raf-1 kinase, and wortmannin had little effect on the activation of MAP kinase by insulin. |
| 355 | 9133538 | These results indicate that 1) PI3-kinase or wortmannin-sensitive molecules are involved in the interaction between activated Ras and Raf-1 kinase in the insulin signaling in 3T3-L1 adipocytes, 2) the involvement of PI3-kinase or wortmannin-sensitive molecules in the insulin-induced activation of MAP kinase appears to be cell-type specific, and 3) differential mechanisms to activate Raf-1 kinase and MAP kinase by insulin and EGF exist. |
| 356 | 9133538 | Differential activation of mitogen-activated protein kinase by insulin and epidermal growth factor in 3T3-L1 adipocytes: a possible involvement of PI3-kinase in the activation of the MAP kinase by insulin. |
| 357 | 9133538 | Mitogen-activated protein (MAP) kinase plays crucial roles in cell growth and differentiation. |
| 358 | 9133538 | It has recently been shown that the MAP kinase cascade in growth factor signaling diverges and cross-talks with other signaling pathways. |
| 359 | 9133538 | In the present study, we examined the effects of wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3-kinase), on the activation of Ras, Raf-1 kinase, and MAP kinase by insulin and epidermal growth factor (EGF). |
| 360 | 9133538 | The effect of LY294002, a structurally distinct PI3-kinase inhibitor, on the activation of Raf-1 kinase by both ligands was also examined. |
| 361 | 9133538 | In 3T3-L1 adipocytes, 25 nmol/l wortmannin inhibited the insulin-induced activation of Raf-1 kinase to the basal level, whereas the same dose of wortmannin had little effect on the EGF-induced activation of Raf-1 kinase. |
| 362 | 9133538 | One hundred micromol/l LY294002 blocked insulin-induced activation of Raf-1 kinase without affecting EGF-induced activation of this kinase. |
| 363 | 9133538 | Twenty-five nmol/l wortmannin inhibited the insulin-induced activation of MAP kinase to the basal level with no effect on the EGF-induced activation of this kinase. |
| 364 | 9133538 | In contrast, in Chinese hamster ovary cells overexpressing the human insulin receptor (CHO-HIR cells), neither wortmannin nor LY294002 inhibited the insulin-induced activation of Raf-1 kinase, and wortmannin had little effect on the activation of MAP kinase by insulin. |
| 365 | 9133538 | These results indicate that 1) PI3-kinase or wortmannin-sensitive molecules are involved in the interaction between activated Ras and Raf-1 kinase in the insulin signaling in 3T3-L1 adipocytes, 2) the involvement of PI3-kinase or wortmannin-sensitive molecules in the insulin-induced activation of MAP kinase appears to be cell-type specific, and 3) differential mechanisms to activate Raf-1 kinase and MAP kinase by insulin and EGF exist. |
| 366 | 9133538 | Differential activation of mitogen-activated protein kinase by insulin and epidermal growth factor in 3T3-L1 adipocytes: a possible involvement of PI3-kinase in the activation of the MAP kinase by insulin. |
| 367 | 9133538 | Mitogen-activated protein (MAP) kinase plays crucial roles in cell growth and differentiation. |
| 368 | 9133538 | It has recently been shown that the MAP kinase cascade in growth factor signaling diverges and cross-talks with other signaling pathways. |
| 369 | 9133538 | In the present study, we examined the effects of wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3-kinase), on the activation of Ras, Raf-1 kinase, and MAP kinase by insulin and epidermal growth factor (EGF). |
| 370 | 9133538 | The effect of LY294002, a structurally distinct PI3-kinase inhibitor, on the activation of Raf-1 kinase by both ligands was also examined. |
| 371 | 9133538 | In 3T3-L1 adipocytes, 25 nmol/l wortmannin inhibited the insulin-induced activation of Raf-1 kinase to the basal level, whereas the same dose of wortmannin had little effect on the EGF-induced activation of Raf-1 kinase. |
| 372 | 9133538 | One hundred micromol/l LY294002 blocked insulin-induced activation of Raf-1 kinase without affecting EGF-induced activation of this kinase. |
| 373 | 9133538 | Twenty-five nmol/l wortmannin inhibited the insulin-induced activation of MAP kinase to the basal level with no effect on the EGF-induced activation of this kinase. |
| 374 | 9133538 | In contrast, in Chinese hamster ovary cells overexpressing the human insulin receptor (CHO-HIR cells), neither wortmannin nor LY294002 inhibited the insulin-induced activation of Raf-1 kinase, and wortmannin had little effect on the activation of MAP kinase by insulin. |
| 375 | 9133538 | These results indicate that 1) PI3-kinase or wortmannin-sensitive molecules are involved in the interaction between activated Ras and Raf-1 kinase in the insulin signaling in 3T3-L1 adipocytes, 2) the involvement of PI3-kinase or wortmannin-sensitive molecules in the insulin-induced activation of MAP kinase appears to be cell-type specific, and 3) differential mechanisms to activate Raf-1 kinase and MAP kinase by insulin and EGF exist. |
| 376 | 9133538 | Differential activation of mitogen-activated protein kinase by insulin and epidermal growth factor in 3T3-L1 adipocytes: a possible involvement of PI3-kinase in the activation of the MAP kinase by insulin. |
| 377 | 9133538 | Mitogen-activated protein (MAP) kinase plays crucial roles in cell growth and differentiation. |
| 378 | 9133538 | It has recently been shown that the MAP kinase cascade in growth factor signaling diverges and cross-talks with other signaling pathways. |
| 379 | 9133538 | In the present study, we examined the effects of wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3-kinase), on the activation of Ras, Raf-1 kinase, and MAP kinase by insulin and epidermal growth factor (EGF). |
| 380 | 9133538 | The effect of LY294002, a structurally distinct PI3-kinase inhibitor, on the activation of Raf-1 kinase by both ligands was also examined. |
| 381 | 9133538 | In 3T3-L1 adipocytes, 25 nmol/l wortmannin inhibited the insulin-induced activation of Raf-1 kinase to the basal level, whereas the same dose of wortmannin had little effect on the EGF-induced activation of Raf-1 kinase. |
| 382 | 9133538 | One hundred micromol/l LY294002 blocked insulin-induced activation of Raf-1 kinase without affecting EGF-induced activation of this kinase. |
| 383 | 9133538 | Twenty-five nmol/l wortmannin inhibited the insulin-induced activation of MAP kinase to the basal level with no effect on the EGF-induced activation of this kinase. |
| 384 | 9133538 | In contrast, in Chinese hamster ovary cells overexpressing the human insulin receptor (CHO-HIR cells), neither wortmannin nor LY294002 inhibited the insulin-induced activation of Raf-1 kinase, and wortmannin had little effect on the activation of MAP kinase by insulin. |
| 385 | 9133538 | These results indicate that 1) PI3-kinase or wortmannin-sensitive molecules are involved in the interaction between activated Ras and Raf-1 kinase in the insulin signaling in 3T3-L1 adipocytes, 2) the involvement of PI3-kinase or wortmannin-sensitive molecules in the insulin-induced activation of MAP kinase appears to be cell-type specific, and 3) differential mechanisms to activate Raf-1 kinase and MAP kinase by insulin and EGF exist. |
| 386 | 9133538 | Differential activation of mitogen-activated protein kinase by insulin and epidermal growth factor in 3T3-L1 adipocytes: a possible involvement of PI3-kinase in the activation of the MAP kinase by insulin. |
| 387 | 9133538 | Mitogen-activated protein (MAP) kinase plays crucial roles in cell growth and differentiation. |
| 388 | 9133538 | It has recently been shown that the MAP kinase cascade in growth factor signaling diverges and cross-talks with other signaling pathways. |
| 389 | 9133538 | In the present study, we examined the effects of wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3-kinase), on the activation of Ras, Raf-1 kinase, and MAP kinase by insulin and epidermal growth factor (EGF). |
| 390 | 9133538 | The effect of LY294002, a structurally distinct PI3-kinase inhibitor, on the activation of Raf-1 kinase by both ligands was also examined. |
| 391 | 9133538 | In 3T3-L1 adipocytes, 25 nmol/l wortmannin inhibited the insulin-induced activation of Raf-1 kinase to the basal level, whereas the same dose of wortmannin had little effect on the EGF-induced activation of Raf-1 kinase. |
| 392 | 9133538 | One hundred micromol/l LY294002 blocked insulin-induced activation of Raf-1 kinase without affecting EGF-induced activation of this kinase. |
| 393 | 9133538 | Twenty-five nmol/l wortmannin inhibited the insulin-induced activation of MAP kinase to the basal level with no effect on the EGF-induced activation of this kinase. |
| 394 | 9133538 | In contrast, in Chinese hamster ovary cells overexpressing the human insulin receptor (CHO-HIR cells), neither wortmannin nor LY294002 inhibited the insulin-induced activation of Raf-1 kinase, and wortmannin had little effect on the activation of MAP kinase by insulin. |
| 395 | 9133538 | These results indicate that 1) PI3-kinase or wortmannin-sensitive molecules are involved in the interaction between activated Ras and Raf-1 kinase in the insulin signaling in 3T3-L1 adipocytes, 2) the involvement of PI3-kinase or wortmannin-sensitive molecules in the insulin-induced activation of MAP kinase appears to be cell-type specific, and 3) differential mechanisms to activate Raf-1 kinase and MAP kinase by insulin and EGF exist. |
| 396 | 9133538 | Differential activation of mitogen-activated protein kinase by insulin and epidermal growth factor in 3T3-L1 adipocytes: a possible involvement of PI3-kinase in the activation of the MAP kinase by insulin. |
| 397 | 9133538 | Mitogen-activated protein (MAP) kinase plays crucial roles in cell growth and differentiation. |
| 398 | 9133538 | It has recently been shown that the MAP kinase cascade in growth factor signaling diverges and cross-talks with other signaling pathways. |
| 399 | 9133538 | In the present study, we examined the effects of wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3-kinase), on the activation of Ras, Raf-1 kinase, and MAP kinase by insulin and epidermal growth factor (EGF). |
| 400 | 9133538 | The effect of LY294002, a structurally distinct PI3-kinase inhibitor, on the activation of Raf-1 kinase by both ligands was also examined. |
| 401 | 9133538 | In 3T3-L1 adipocytes, 25 nmol/l wortmannin inhibited the insulin-induced activation of Raf-1 kinase to the basal level, whereas the same dose of wortmannin had little effect on the EGF-induced activation of Raf-1 kinase. |
| 402 | 9133538 | One hundred micromol/l LY294002 blocked insulin-induced activation of Raf-1 kinase without affecting EGF-induced activation of this kinase. |
| 403 | 9133538 | Twenty-five nmol/l wortmannin inhibited the insulin-induced activation of MAP kinase to the basal level with no effect on the EGF-induced activation of this kinase. |
| 404 | 9133538 | In contrast, in Chinese hamster ovary cells overexpressing the human insulin receptor (CHO-HIR cells), neither wortmannin nor LY294002 inhibited the insulin-induced activation of Raf-1 kinase, and wortmannin had little effect on the activation of MAP kinase by insulin. |
| 405 | 9133538 | These results indicate that 1) PI3-kinase or wortmannin-sensitive molecules are involved in the interaction between activated Ras and Raf-1 kinase in the insulin signaling in 3T3-L1 adipocytes, 2) the involvement of PI3-kinase or wortmannin-sensitive molecules in the insulin-induced activation of MAP kinase appears to be cell-type specific, and 3) differential mechanisms to activate Raf-1 kinase and MAP kinase by insulin and EGF exist. |
| 406 | 9165048 | Mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways are not sufficient for insulin-like growth factor I-induced mitogenesis and tumorigenesis. |
| 407 | 9165048 | Insulin-like growth factor-I (IGF-I) and insulin are known to activate a signaling cascade involving ras --> kappa raf-1 --> mitogen-activated protein (MAP) kinase kinase (MEK) --> p42/p44 MAP kinase (Erk-1 and -2). |
| 408 | 9165048 | Recent reports suggest that activation of this ras/MAP kinase pathway is involved in mitogenesis and c-fos transcription but is not required for insulin action on metabolic processes such as glycogen synthesis, lipogenesis, and GLUT-4-mediated glucose transport. |
| 409 | 9165048 | To further characterize the role of these tyrosines in IGF-I receptor function, we have used three distinct approaches to examine the ras/MAP kinase pathway in IGF-I-induced mitogenesis and tumorigenesis in NIH-3T3 cells overexpressing wild-type and mutated IGF-I receptors: 1) tyrosine phosphorylation of the MAP kinases Erk-1 and -2; 2), mobility shifts indicative of MAP kinase phosphorylation; and 3) in vitro MAP kinase activation. |
| 410 | 9165048 | By each method we show that the IGF-I-induced MAP kinase phosphorylation/activation and PI 3-kinase activation, are not different between cells overexpressing wild-type IGF-I receptors and cells carrying IGF-I receptors having tyrosine motifs replaced at positions 1250 and 1251. |
| 411 | 9165048 | We conclude that mitogenic and tumorigenic signals involving tyrosine residues in the C-terminal domain of the IGF-I-receptor include pathways other than the MAP kinase and PI 3-kinase pathways. |
| 412 | 9165048 | Mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways are not sufficient for insulin-like growth factor I-induced mitogenesis and tumorigenesis. |
| 413 | 9165048 | Insulin-like growth factor-I (IGF-I) and insulin are known to activate a signaling cascade involving ras --> kappa raf-1 --> mitogen-activated protein (MAP) kinase kinase (MEK) --> p42/p44 MAP kinase (Erk-1 and -2). |
| 414 | 9165048 | Recent reports suggest that activation of this ras/MAP kinase pathway is involved in mitogenesis and c-fos transcription but is not required for insulin action on metabolic processes such as glycogen synthesis, lipogenesis, and GLUT-4-mediated glucose transport. |
| 415 | 9165048 | To further characterize the role of these tyrosines in IGF-I receptor function, we have used three distinct approaches to examine the ras/MAP kinase pathway in IGF-I-induced mitogenesis and tumorigenesis in NIH-3T3 cells overexpressing wild-type and mutated IGF-I receptors: 1) tyrosine phosphorylation of the MAP kinases Erk-1 and -2; 2), mobility shifts indicative of MAP kinase phosphorylation; and 3) in vitro MAP kinase activation. |
| 416 | 9165048 | By each method we show that the IGF-I-induced MAP kinase phosphorylation/activation and PI 3-kinase activation, are not different between cells overexpressing wild-type IGF-I receptors and cells carrying IGF-I receptors having tyrosine motifs replaced at positions 1250 and 1251. |
| 417 | 9165048 | We conclude that mitogenic and tumorigenic signals involving tyrosine residues in the C-terminal domain of the IGF-I-receptor include pathways other than the MAP kinase and PI 3-kinase pathways. |
| 418 | 9165048 | Mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways are not sufficient for insulin-like growth factor I-induced mitogenesis and tumorigenesis. |
| 419 | 9165048 | Insulin-like growth factor-I (IGF-I) and insulin are known to activate a signaling cascade involving ras --> kappa raf-1 --> mitogen-activated protein (MAP) kinase kinase (MEK) --> p42/p44 MAP kinase (Erk-1 and -2). |
| 420 | 9165048 | Recent reports suggest that activation of this ras/MAP kinase pathway is involved in mitogenesis and c-fos transcription but is not required for insulin action on metabolic processes such as glycogen synthesis, lipogenesis, and GLUT-4-mediated glucose transport. |
| 421 | 9165048 | To further characterize the role of these tyrosines in IGF-I receptor function, we have used three distinct approaches to examine the ras/MAP kinase pathway in IGF-I-induced mitogenesis and tumorigenesis in NIH-3T3 cells overexpressing wild-type and mutated IGF-I receptors: 1) tyrosine phosphorylation of the MAP kinases Erk-1 and -2; 2), mobility shifts indicative of MAP kinase phosphorylation; and 3) in vitro MAP kinase activation. |
| 422 | 9165048 | By each method we show that the IGF-I-induced MAP kinase phosphorylation/activation and PI 3-kinase activation, are not different between cells overexpressing wild-type IGF-I receptors and cells carrying IGF-I receptors having tyrosine motifs replaced at positions 1250 and 1251. |
| 423 | 9165048 | We conclude that mitogenic and tumorigenic signals involving tyrosine residues in the C-terminal domain of the IGF-I-receptor include pathways other than the MAP kinase and PI 3-kinase pathways. |
| 424 | 9165048 | Mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways are not sufficient for insulin-like growth factor I-induced mitogenesis and tumorigenesis. |
| 425 | 9165048 | Insulin-like growth factor-I (IGF-I) and insulin are known to activate a signaling cascade involving ras --> kappa raf-1 --> mitogen-activated protein (MAP) kinase kinase (MEK) --> p42/p44 MAP kinase (Erk-1 and -2). |
| 426 | 9165048 | Recent reports suggest that activation of this ras/MAP kinase pathway is involved in mitogenesis and c-fos transcription but is not required for insulin action on metabolic processes such as glycogen synthesis, lipogenesis, and GLUT-4-mediated glucose transport. |
| 427 | 9165048 | To further characterize the role of these tyrosines in IGF-I receptor function, we have used three distinct approaches to examine the ras/MAP kinase pathway in IGF-I-induced mitogenesis and tumorigenesis in NIH-3T3 cells overexpressing wild-type and mutated IGF-I receptors: 1) tyrosine phosphorylation of the MAP kinases Erk-1 and -2; 2), mobility shifts indicative of MAP kinase phosphorylation; and 3) in vitro MAP kinase activation. |
| 428 | 9165048 | By each method we show that the IGF-I-induced MAP kinase phosphorylation/activation and PI 3-kinase activation, are not different between cells overexpressing wild-type IGF-I receptors and cells carrying IGF-I receptors having tyrosine motifs replaced at positions 1250 and 1251. |
| 429 | 9165048 | We conclude that mitogenic and tumorigenic signals involving tyrosine residues in the C-terminal domain of the IGF-I-receptor include pathways other than the MAP kinase and PI 3-kinase pathways. |
| 430 | 9165048 | Mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways are not sufficient for insulin-like growth factor I-induced mitogenesis and tumorigenesis. |
| 431 | 9165048 | Insulin-like growth factor-I (IGF-I) and insulin are known to activate a signaling cascade involving ras --> kappa raf-1 --> mitogen-activated protein (MAP) kinase kinase (MEK) --> p42/p44 MAP kinase (Erk-1 and -2). |
| 432 | 9165048 | Recent reports suggest that activation of this ras/MAP kinase pathway is involved in mitogenesis and c-fos transcription but is not required for insulin action on metabolic processes such as glycogen synthesis, lipogenesis, and GLUT-4-mediated glucose transport. |
| 433 | 9165048 | To further characterize the role of these tyrosines in IGF-I receptor function, we have used three distinct approaches to examine the ras/MAP kinase pathway in IGF-I-induced mitogenesis and tumorigenesis in NIH-3T3 cells overexpressing wild-type and mutated IGF-I receptors: 1) tyrosine phosphorylation of the MAP kinases Erk-1 and -2; 2), mobility shifts indicative of MAP kinase phosphorylation; and 3) in vitro MAP kinase activation. |
| 434 | 9165048 | By each method we show that the IGF-I-induced MAP kinase phosphorylation/activation and PI 3-kinase activation, are not different between cells overexpressing wild-type IGF-I receptors and cells carrying IGF-I receptors having tyrosine motifs replaced at positions 1250 and 1251. |
| 435 | 9165048 | We conclude that mitogenic and tumorigenic signals involving tyrosine residues in the C-terminal domain of the IGF-I-receptor include pathways other than the MAP kinase and PI 3-kinase pathways. |
| 436 | 9169593 | Insulin regulation of mitogen-activated protein kinase kinase (MEK), mitogen-activated protein kinase and casein kinase in the cell nucleus: a possible role in the regulation of gene expression. |
| 437 | 9169593 | After insulin receptor activation, many cytoplasmic enzymes, including mitogen-activated protein (MAP) kinase, MAP kinase kinase (MEK) and casein kinase II (CKII) are activated, but exactly how insulin signalling progresses to the nucleus remains poorly understood. |
| 438 | 9169593 | In Chinese hamster ovary cells overexpressing human insulin receptors [CHO(Hirc)], MEK, CKII and the MAP kinases ERK I and ERK II can be detected by immunoblotting in the nucleus, as well as in the cytoplasm, in the unstimulated state. |
| 439 | 9169593 | Nuclear localization of MAP kinase is also observed in 3T3-F442A adipocytes, NIH-3T3 cells and Fao hepatoma cells, whereas MEK is found in the nucleus only in Fao and CHO cells. |
| 440 | 9169593 | Insulin treatment for 5-30 min induces a translocation of MEK from the cytoplasm to the nucleus, whereas the MAP kinases and CKII are not translocated into the nucleus in response to insulin during this period. |
| 441 | 9169593 | However, nuclear MAP kinase and CKII activities increase by 2-3-fold within 1-10 min after stimulation with insulin. |
| 442 | 9169593 | By using gel-shift assays, it has been shown that insulin also stimulates nuclear protein binding to an AP-1 site with kinetics similar to MEK translocation and MAP kinase and CKII activation. |
| 443 | 9169593 | Treatment of the extracts in vitro with protein phosphatase 2A or treatment of the intact cells with 5, 6-dichloro-1-beta-d-ribofuranosylbenzimidazole, a cell-permeable inhibitor of CKII, almost completely blocks the insulin-induced DNA-binding activity, whereas incubation of cells with a MEK inhibitor produces only a slight decrease. |
| 444 | 9169593 | The latter is true of CKII, which seems to regulate the binding of nuclear proteins to the AP-1 site, possibly by phosphorylation of AP-1 transcription factors. |
| 445 | 9169593 | Insulin regulation of mitogen-activated protein kinase kinase (MEK), mitogen-activated protein kinase and casein kinase in the cell nucleus: a possible role in the regulation of gene expression. |
| 446 | 9169593 | After insulin receptor activation, many cytoplasmic enzymes, including mitogen-activated protein (MAP) kinase, MAP kinase kinase (MEK) and casein kinase II (CKII) are activated, but exactly how insulin signalling progresses to the nucleus remains poorly understood. |
| 447 | 9169593 | In Chinese hamster ovary cells overexpressing human insulin receptors [CHO(Hirc)], MEK, CKII and the MAP kinases ERK I and ERK II can be detected by immunoblotting in the nucleus, as well as in the cytoplasm, in the unstimulated state. |
| 448 | 9169593 | Nuclear localization of MAP kinase is also observed in 3T3-F442A adipocytes, NIH-3T3 cells and Fao hepatoma cells, whereas MEK is found in the nucleus only in Fao and CHO cells. |
| 449 | 9169593 | Insulin treatment for 5-30 min induces a translocation of MEK from the cytoplasm to the nucleus, whereas the MAP kinases and CKII are not translocated into the nucleus in response to insulin during this period. |
| 450 | 9169593 | However, nuclear MAP kinase and CKII activities increase by 2-3-fold within 1-10 min after stimulation with insulin. |
| 451 | 9169593 | By using gel-shift assays, it has been shown that insulin also stimulates nuclear protein binding to an AP-1 site with kinetics similar to MEK translocation and MAP kinase and CKII activation. |
| 452 | 9169593 | Treatment of the extracts in vitro with protein phosphatase 2A or treatment of the intact cells with 5, 6-dichloro-1-beta-d-ribofuranosylbenzimidazole, a cell-permeable inhibitor of CKII, almost completely blocks the insulin-induced DNA-binding activity, whereas incubation of cells with a MEK inhibitor produces only a slight decrease. |
| 453 | 9169593 | The latter is true of CKII, which seems to regulate the binding of nuclear proteins to the AP-1 site, possibly by phosphorylation of AP-1 transcription factors. |
| 454 | 9169593 | Insulin regulation of mitogen-activated protein kinase kinase (MEK), mitogen-activated protein kinase and casein kinase in the cell nucleus: a possible role in the regulation of gene expression. |
| 455 | 9169593 | After insulin receptor activation, many cytoplasmic enzymes, including mitogen-activated protein (MAP) kinase, MAP kinase kinase (MEK) and casein kinase II (CKII) are activated, but exactly how insulin signalling progresses to the nucleus remains poorly understood. |
| 456 | 9169593 | In Chinese hamster ovary cells overexpressing human insulin receptors [CHO(Hirc)], MEK, CKII and the MAP kinases ERK I and ERK II can be detected by immunoblotting in the nucleus, as well as in the cytoplasm, in the unstimulated state. |
| 457 | 9169593 | Nuclear localization of MAP kinase is also observed in 3T3-F442A adipocytes, NIH-3T3 cells and Fao hepatoma cells, whereas MEK is found in the nucleus only in Fao and CHO cells. |
| 458 | 9169593 | Insulin treatment for 5-30 min induces a translocation of MEK from the cytoplasm to the nucleus, whereas the MAP kinases and CKII are not translocated into the nucleus in response to insulin during this period. |
| 459 | 9169593 | However, nuclear MAP kinase and CKII activities increase by 2-3-fold within 1-10 min after stimulation with insulin. |
| 460 | 9169593 | By using gel-shift assays, it has been shown that insulin also stimulates nuclear protein binding to an AP-1 site with kinetics similar to MEK translocation and MAP kinase and CKII activation. |
| 461 | 9169593 | Treatment of the extracts in vitro with protein phosphatase 2A or treatment of the intact cells with 5, 6-dichloro-1-beta-d-ribofuranosylbenzimidazole, a cell-permeable inhibitor of CKII, almost completely blocks the insulin-induced DNA-binding activity, whereas incubation of cells with a MEK inhibitor produces only a slight decrease. |
| 462 | 9169593 | The latter is true of CKII, which seems to regulate the binding of nuclear proteins to the AP-1 site, possibly by phosphorylation of AP-1 transcription factors. |
| 463 | 9169593 | Insulin regulation of mitogen-activated protein kinase kinase (MEK), mitogen-activated protein kinase and casein kinase in the cell nucleus: a possible role in the regulation of gene expression. |
| 464 | 9169593 | After insulin receptor activation, many cytoplasmic enzymes, including mitogen-activated protein (MAP) kinase, MAP kinase kinase (MEK) and casein kinase II (CKII) are activated, but exactly how insulin signalling progresses to the nucleus remains poorly understood. |
| 465 | 9169593 | In Chinese hamster ovary cells overexpressing human insulin receptors [CHO(Hirc)], MEK, CKII and the MAP kinases ERK I and ERK II can be detected by immunoblotting in the nucleus, as well as in the cytoplasm, in the unstimulated state. |
| 466 | 9169593 | Nuclear localization of MAP kinase is also observed in 3T3-F442A adipocytes, NIH-3T3 cells and Fao hepatoma cells, whereas MEK is found in the nucleus only in Fao and CHO cells. |
| 467 | 9169593 | Insulin treatment for 5-30 min induces a translocation of MEK from the cytoplasm to the nucleus, whereas the MAP kinases and CKII are not translocated into the nucleus in response to insulin during this period. |
| 468 | 9169593 | However, nuclear MAP kinase and CKII activities increase by 2-3-fold within 1-10 min after stimulation with insulin. |
| 469 | 9169593 | By using gel-shift assays, it has been shown that insulin also stimulates nuclear protein binding to an AP-1 site with kinetics similar to MEK translocation and MAP kinase and CKII activation. |
| 470 | 9169593 | Treatment of the extracts in vitro with protein phosphatase 2A or treatment of the intact cells with 5, 6-dichloro-1-beta-d-ribofuranosylbenzimidazole, a cell-permeable inhibitor of CKII, almost completely blocks the insulin-induced DNA-binding activity, whereas incubation of cells with a MEK inhibitor produces only a slight decrease. |
| 471 | 9169593 | The latter is true of CKII, which seems to regulate the binding of nuclear proteins to the AP-1 site, possibly by phosphorylation of AP-1 transcription factors. |
| 472 | 9175762 | The proto-oncogene Crk-II enhances apoptosis by a Ras-dependent, Raf-1/MAP kinase-independent pathway. |
| 473 | 9175762 | The results presented here suggest that overexpression of Crk-II induces apoptosis via a Ras-dependent, Raf-1/MEK1/ERK-independent pathway. |
| 474 | 9195921 | SPP was found to strongly induce tyrosine phosphorylation of Crk, but not Shc, in NIH-3T3 parental, insulin-like growth factor-I receptor-overexpressing and Crk-overexpressing (3T3-Crk) fibroblasts. |
| 475 | 9195921 | This stimulation appears to be Ras-dependent, whereas SPP stimulation of MAP kinase activity is Ras-independent. |
| 476 | 9435680 | Bradykinin induces tubulin phosphorylation and nuclear translocation of MAP kinase in mesangial cells. |
| 477 | 9518262 | Overexpression of membrane glycoprotein PC-1 can influence insulin action at a post-receptor site. |
| 478 | 9518262 | An elevated content of membrane glycoprotein PC-1 has been observed in cells and tissues of insulin resistant patients. |
| 479 | 9518262 | In addition, in vitro overexpression of PC-1 in cultured cells induces insulin resistance associated with diminished insulin receptor tyrosine kinase activity. |
| 480 | 9518262 | We now find that PC-1 overexpression also influences insulin receptor signaling at a step downstream of insulin receptor tyrosine kinase, independent of insulin receptor tyrosine kinase. |
| 481 | 9518262 | In the present studies, we employed Chinese hamster ovary cells that overexpress the human insulin receptor (CHO IR cells; approximately 10(6) receptors per cell), and transfected them with human PC-1 c-DNA (CHO IR PC-1). |
| 482 | 9518262 | In CHO IR PC-1 cells, insulin receptor tyrosine kinase activity was unchanged, following insulin treatment of cells. |
| 483 | 9518262 | In CHO IR PC-1 cells, insulin stimulation of mitogen-activated protein (MAP) kinase activity was normal, suggesting that PC-1 overexpression did not affect insulin receptor activation of Ras, which is upstream of MAP kinase. |
| 484 | 9518262 | Also, insulin-stimulated phosphatidylinositol (PI)-3-kinase activity was normal, suggesting that PC-1 overexpression did not interfere with the activation of this enzyme by insulin receptor substrate-1. |
| 485 | 9518262 | In these cells, however, insulin stimulation of p70 ribosomal S6 kinase activity was diminished. |
| 486 | 9518262 | These studies suggest, therefore, that, in addition to blocking insulin receptor tyrosine kinase activation, PC-1 can also block insulin receptor signaling at a post-receptor site. |
| 487 | 9549231 | Effects of diabetes and difluoromethylornithine treatment on hyperplasia, activity of MAP-kinase, and activity and association with cyclin B of p34cdc2 kinase in rat jejunal mucosa. |
| 488 | 9578588 | Vanadyl sulfate-stimulated glycogen synthesis is associated with activation of phosphatidylinositol 3-kinase and is independent of insulin receptor tyrosine phosphorylation. |
| 489 | 9578588 | We have shown earlier that different vanadium salts stimulate the MAP kinase pathway and ribosomal-S-6-kinase (p70s6k) in chinese hamster ovary cells overexpressing human insulin receptor (CHO-HIR cells) [Pandey, S. |
| 490 | 9578588 | In the present studies, we have investigated if similar to insulin, VS also activates phosphatidylinositol 3-kinase (PI3-k) activity, and whether VS-induced activation of the PI3-k, MAP kinase, and p70s6k pathways contributes to glycogen synthesis. |
| 491 | 9578588 | On the other hand, PD98059 and rapamycin, specific inhibitors of the MAP kinase pathway and p70s6k, respectively, were unable to inhibit VS-stimulated glycogen synthesis. |
| 492 | 9578588 | Moreover, VS-stimulated glycogen synthesis and PI3-k were observed without any change in the tyrosine phosphorylation of insulin receptor (IR) beta-subunit but were associated with increased tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1). |
| 493 | 9578588 | In addition, PI3-k activation was detected in IRS-1 immunoprecipitates from VS-stimulated cells, indicating that tyrosine-phosphorylated IRS-1 was able to interact and thereby activate PI3-k in response to VS. |
| 494 | 9578588 | Taken together, these results provide evidence that tyrosine phosphorylation of IRS-1 and activation of PI3-k play a key role in mediating the insulinomimetic effect of VS on glycogen synthesis independent of IR-tyrosine phosphorylation. |
| 495 | 9578588 | Vanadyl sulfate-stimulated glycogen synthesis is associated with activation of phosphatidylinositol 3-kinase and is independent of insulin receptor tyrosine phosphorylation. |
| 496 | 9578588 | We have shown earlier that different vanadium salts stimulate the MAP kinase pathway and ribosomal-S-6-kinase (p70s6k) in chinese hamster ovary cells overexpressing human insulin receptor (CHO-HIR cells) [Pandey, S. |
| 497 | 9578588 | In the present studies, we have investigated if similar to insulin, VS also activates phosphatidylinositol 3-kinase (PI3-k) activity, and whether VS-induced activation of the PI3-k, MAP kinase, and p70s6k pathways contributes to glycogen synthesis. |
| 498 | 9578588 | On the other hand, PD98059 and rapamycin, specific inhibitors of the MAP kinase pathway and p70s6k, respectively, were unable to inhibit VS-stimulated glycogen synthesis. |
| 499 | 9578588 | Moreover, VS-stimulated glycogen synthesis and PI3-k were observed without any change in the tyrosine phosphorylation of insulin receptor (IR) beta-subunit but were associated with increased tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1). |
| 500 | 9578588 | In addition, PI3-k activation was detected in IRS-1 immunoprecipitates from VS-stimulated cells, indicating that tyrosine-phosphorylated IRS-1 was able to interact and thereby activate PI3-k in response to VS. |
| 501 | 9578588 | Taken together, these results provide evidence that tyrosine phosphorylation of IRS-1 and activation of PI3-k play a key role in mediating the insulinomimetic effect of VS on glycogen synthesis independent of IR-tyrosine phosphorylation. |
| 502 | 9578588 | Vanadyl sulfate-stimulated glycogen synthesis is associated with activation of phosphatidylinositol 3-kinase and is independent of insulin receptor tyrosine phosphorylation. |
| 503 | 9578588 | We have shown earlier that different vanadium salts stimulate the MAP kinase pathway and ribosomal-S-6-kinase (p70s6k) in chinese hamster ovary cells overexpressing human insulin receptor (CHO-HIR cells) [Pandey, S. |
| 504 | 9578588 | In the present studies, we have investigated if similar to insulin, VS also activates phosphatidylinositol 3-kinase (PI3-k) activity, and whether VS-induced activation of the PI3-k, MAP kinase, and p70s6k pathways contributes to glycogen synthesis. |
| 505 | 9578588 | On the other hand, PD98059 and rapamycin, specific inhibitors of the MAP kinase pathway and p70s6k, respectively, were unable to inhibit VS-stimulated glycogen synthesis. |
| 506 | 9578588 | Moreover, VS-stimulated glycogen synthesis and PI3-k were observed without any change in the tyrosine phosphorylation of insulin receptor (IR) beta-subunit but were associated with increased tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1). |
| 507 | 9578588 | In addition, PI3-k activation was detected in IRS-1 immunoprecipitates from VS-stimulated cells, indicating that tyrosine-phosphorylated IRS-1 was able to interact and thereby activate PI3-k in response to VS. |
| 508 | 9578588 | Taken together, these results provide evidence that tyrosine phosphorylation of IRS-1 and activation of PI3-k play a key role in mediating the insulinomimetic effect of VS on glycogen synthesis independent of IR-tyrosine phosphorylation. |
| 509 | 9609113 | Protein phosphatase-1 and insulin action. |
| 510 | 9609113 | Protein Phosphatase-1 (PP-1) appears to be the key component of the insulin signalling pathway which is responsible for bridging the initial insulin-simulated phosphorylation cascade with the ultimate dephosphorylation of insulin sensitive substrates. |
| 511 | 9609113 | Dephosphorylations catalyzed by PP-1 activate glycogen synthase (GS) and simultaneously inactivate phosphorylase a and phosphorylase kinase promoting glycogen synthesis. |
| 512 | 9609113 | Our in vivo studies using L6 rat skeletal muscle cells and freshly isolated adipocytes indicate that insulin stimulates PP-1 by increasing the phosphorylation status of its regulatory subunit (PP-1G). |
| 513 | 9609113 | PP-1 activation is accompanied by an inactivation of Protein Phosphatase-2A (PP-2A) activity. |
| 514 | 9609113 | To gain insight into the upstream kinases that mediate insulin-stimulated PP-1G phosphorylation, we employed inhibitors of the ras/MAPK, PI3-kinase, and PKC signalling pathways. |
| 515 | 9609113 | These inhibitor studies suggest that PP-1G phosphorylation is mediated via a complex, cell type specific mechanism involving PI3-kinase/PKC/PKB and/or the ras/MAP kinase/Rsk kinase cascade. cAMP agonists such as SpcAMP (via PKA) and TNF-alpha (recently identified as endogenous inhibitor of insulin action via ceramide) block insulin-stimulated PP-1G phosphorylation with a parallel decrease of PP-1 activity, presumably due to the dissociation of the PP-1 catalytic subunit from the regulatory G-subunit. |
| 516 | 9609113 | It appears that any agent or condition which interferes with the insulin-induced phosphorylation and activation of PP-1, will decrease the magnitude of insulin's effect on downstream metabolic processes. |
| 517 | 9609113 | Therefore, regulation of the PP-1G subunit by site-specific phosphorylation plays an important role in insulin signal transduction in target cells. |
| 518 | 9609113 | Mechanistic and functional studies with cell lines expressing PP-1G subunit site-specific mutations will help clarify the exact role and regulation of PP-1G site-specific phosphorylations on PP-1 catalytic function. |
| 519 | 9648831 | A gene candidate approach revealed that mRNA levels of the oncogenes c-fos and c-jun were equivalently expressed in insulinoma and islet cells, as was the mRNA for the mitogenic signal transduction molecule insulin receptor substrate (IRS)-1. |
| 520 | 9648831 | However, in contrast to that of IRS-1, IRS-2 gene expression was 60- to 70-fold higher in the insulinoma tissue compared with islets, which was reflected at the protein as well as the mRNA level. |
| 521 | 9648831 | This serum-stimulated DNA synthesis was prevented by inhibitors of tyrosine protein kinase and phosphatidylinositol (PI) 3-kinase activities, as well as the activation of mitogen-activated protein (MAP) kinase and p70S6K. |
| 522 | 9648831 | Moreover, serum also activated MAP-kinase (erk-1 and erk-2 isoforms) and 70 kD S6 kinase. |
| 523 | 9648831 | A gene candidate approach revealed that mRNA levels of the oncogenes c-fos and c-jun were equivalently expressed in insulinoma and islet cells, as was the mRNA for the mitogenic signal transduction molecule insulin receptor substrate (IRS)-1. |
| 524 | 9648831 | However, in contrast to that of IRS-1, IRS-2 gene expression was 60- to 70-fold higher in the insulinoma tissue compared with islets, which was reflected at the protein as well as the mRNA level. |
| 525 | 9648831 | This serum-stimulated DNA synthesis was prevented by inhibitors of tyrosine protein kinase and phosphatidylinositol (PI) 3-kinase activities, as well as the activation of mitogen-activated protein (MAP) kinase and p70S6K. |
| 526 | 9648831 | Moreover, serum also activated MAP-kinase (erk-1 and erk-2 isoforms) and 70 kD S6 kinase. |
| 527 | 9688610 | The mitogen-activated protein (MAP) kinase signaling pathways are believed to act as critical signal transducers between stress stimuli and transcriptional responses in mammalian cells. |
| 528 | 9688610 | To determine whether injury to the vastus lateralis muscle activates MAP kinase signaling in human subjects, two needle biopsies or open muscle biopsies were taken from the same incision site 30-60 min apart. |
| 529 | 9688610 | The muscle biopsy procedures resulted in striking increases in dual phosphorylation of the extracellular-regulated kinases (ERK1 and ERK2) and in activity of the downstream substrate, the p90 ribosomal S6 kinase. |
| 530 | 9688610 | Raf-1 kinase and MAP kinase kinase, upstream activators of ERK, were also markedly stimulated in all subjects. |
| 531 | 9688610 | In addition, c-Jun NH2-terminal kinase and p38 kinase, components of two parallel MAP kinase pathways, were activated following muscle injury. |
| 532 | 9688610 | The stimulation of the three MAP kinase cascades was present only in the immediate vicinity of the injury, a finding consistent with a local rather than systemic activation of these signaling cascades in response to injury. |
| 533 | 9688610 | These data demonstrate that muscle injury induces the stimulation of the three MAP kinase cascades in human skeletal muscle, suggesting a physiological relevance of these protein kinases in the immediate response to tissue injury and possibly in the initiation of wound healing. |
| 534 | 9688610 | The mitogen-activated protein (MAP) kinase signaling pathways are believed to act as critical signal transducers between stress stimuli and transcriptional responses in mammalian cells. |
| 535 | 9688610 | To determine whether injury to the vastus lateralis muscle activates MAP kinase signaling in human subjects, two needle biopsies or open muscle biopsies were taken from the same incision site 30-60 min apart. |
| 536 | 9688610 | The muscle biopsy procedures resulted in striking increases in dual phosphorylation of the extracellular-regulated kinases (ERK1 and ERK2) and in activity of the downstream substrate, the p90 ribosomal S6 kinase. |
| 537 | 9688610 | Raf-1 kinase and MAP kinase kinase, upstream activators of ERK, were also markedly stimulated in all subjects. |
| 538 | 9688610 | In addition, c-Jun NH2-terminal kinase and p38 kinase, components of two parallel MAP kinase pathways, were activated following muscle injury. |
| 539 | 9688610 | The stimulation of the three MAP kinase cascades was present only in the immediate vicinity of the injury, a finding consistent with a local rather than systemic activation of these signaling cascades in response to injury. |
| 540 | 9688610 | These data demonstrate that muscle injury induces the stimulation of the three MAP kinase cascades in human skeletal muscle, suggesting a physiological relevance of these protein kinases in the immediate response to tissue injury and possibly in the initiation of wound healing. |
| 541 | 9688610 | The mitogen-activated protein (MAP) kinase signaling pathways are believed to act as critical signal transducers between stress stimuli and transcriptional responses in mammalian cells. |
| 542 | 9688610 | To determine whether injury to the vastus lateralis muscle activates MAP kinase signaling in human subjects, two needle biopsies or open muscle biopsies were taken from the same incision site 30-60 min apart. |
| 543 | 9688610 | The muscle biopsy procedures resulted in striking increases in dual phosphorylation of the extracellular-regulated kinases (ERK1 and ERK2) and in activity of the downstream substrate, the p90 ribosomal S6 kinase. |
| 544 | 9688610 | Raf-1 kinase and MAP kinase kinase, upstream activators of ERK, were also markedly stimulated in all subjects. |
| 545 | 9688610 | In addition, c-Jun NH2-terminal kinase and p38 kinase, components of two parallel MAP kinase pathways, were activated following muscle injury. |
| 546 | 9688610 | The stimulation of the three MAP kinase cascades was present only in the immediate vicinity of the injury, a finding consistent with a local rather than systemic activation of these signaling cascades in response to injury. |
| 547 | 9688610 | These data demonstrate that muscle injury induces the stimulation of the three MAP kinase cascades in human skeletal muscle, suggesting a physiological relevance of these protein kinases in the immediate response to tissue injury and possibly in the initiation of wound healing. |
| 548 | 9688610 | The mitogen-activated protein (MAP) kinase signaling pathways are believed to act as critical signal transducers between stress stimuli and transcriptional responses in mammalian cells. |
| 549 | 9688610 | To determine whether injury to the vastus lateralis muscle activates MAP kinase signaling in human subjects, two needle biopsies or open muscle biopsies were taken from the same incision site 30-60 min apart. |
| 550 | 9688610 | The muscle biopsy procedures resulted in striking increases in dual phosphorylation of the extracellular-regulated kinases (ERK1 and ERK2) and in activity of the downstream substrate, the p90 ribosomal S6 kinase. |
| 551 | 9688610 | Raf-1 kinase and MAP kinase kinase, upstream activators of ERK, were also markedly stimulated in all subjects. |
| 552 | 9688610 | In addition, c-Jun NH2-terminal kinase and p38 kinase, components of two parallel MAP kinase pathways, were activated following muscle injury. |
| 553 | 9688610 | The stimulation of the three MAP kinase cascades was present only in the immediate vicinity of the injury, a finding consistent with a local rather than systemic activation of these signaling cascades in response to injury. |
| 554 | 9688610 | These data demonstrate that muscle injury induces the stimulation of the three MAP kinase cascades in human skeletal muscle, suggesting a physiological relevance of these protein kinases in the immediate response to tissue injury and possibly in the initiation of wound healing. |
| 555 | 9688610 | The mitogen-activated protein (MAP) kinase signaling pathways are believed to act as critical signal transducers between stress stimuli and transcriptional responses in mammalian cells. |
| 556 | 9688610 | To determine whether injury to the vastus lateralis muscle activates MAP kinase signaling in human subjects, two needle biopsies or open muscle biopsies were taken from the same incision site 30-60 min apart. |
| 557 | 9688610 | The muscle biopsy procedures resulted in striking increases in dual phosphorylation of the extracellular-regulated kinases (ERK1 and ERK2) and in activity of the downstream substrate, the p90 ribosomal S6 kinase. |
| 558 | 9688610 | Raf-1 kinase and MAP kinase kinase, upstream activators of ERK, were also markedly stimulated in all subjects. |
| 559 | 9688610 | In addition, c-Jun NH2-terminal kinase and p38 kinase, components of two parallel MAP kinase pathways, were activated following muscle injury. |
| 560 | 9688610 | The stimulation of the three MAP kinase cascades was present only in the immediate vicinity of the injury, a finding consistent with a local rather than systemic activation of these signaling cascades in response to injury. |
| 561 | 9688610 | These data demonstrate that muscle injury induces the stimulation of the three MAP kinase cascades in human skeletal muscle, suggesting a physiological relevance of these protein kinases in the immediate response to tissue injury and possibly in the initiation of wound healing. |
| 562 | 9688610 | The mitogen-activated protein (MAP) kinase signaling pathways are believed to act as critical signal transducers between stress stimuli and transcriptional responses in mammalian cells. |
| 563 | 9688610 | To determine whether injury to the vastus lateralis muscle activates MAP kinase signaling in human subjects, two needle biopsies or open muscle biopsies were taken from the same incision site 30-60 min apart. |
| 564 | 9688610 | The muscle biopsy procedures resulted in striking increases in dual phosphorylation of the extracellular-regulated kinases (ERK1 and ERK2) and in activity of the downstream substrate, the p90 ribosomal S6 kinase. |
| 565 | 9688610 | Raf-1 kinase and MAP kinase kinase, upstream activators of ERK, were also markedly stimulated in all subjects. |
| 566 | 9688610 | In addition, c-Jun NH2-terminal kinase and p38 kinase, components of two parallel MAP kinase pathways, were activated following muscle injury. |
| 567 | 9688610 | The stimulation of the three MAP kinase cascades was present only in the immediate vicinity of the injury, a finding consistent with a local rather than systemic activation of these signaling cascades in response to injury. |
| 568 | 9688610 | These data demonstrate that muscle injury induces the stimulation of the three MAP kinase cascades in human skeletal muscle, suggesting a physiological relevance of these protein kinases in the immediate response to tissue injury and possibly in the initiation of wound healing. |
| 569 | 9753291 | Little is known about the regulation of the mitogen-activated protein (MAP) kinase signaling cascades by hormonal stimulation in vivo. |
| 570 | 9753291 | The extracellular signal-regulated kinase (ERK) and the c-jun kinase (JNK) are two MAP kinase signaling pathways that could play a role in the cellular response to hormones such as insulin and epinephrine. |
| 571 | 9753291 | We studied the effects of insulin (20 U/rat) and epinephrine (25 microg/100 g body wt) injected in vivo on ERK and JNK signaling in skeletal muscle from Sprague-Dawley rats. |
| 572 | 9753291 | Insulin significantly increased ERK phosphorylation and the activity of its downstream substrate, the p90 ribosomal S6 kinase 2 (RSK2), by 1.4-fold, but it had no effect on JNK activity. |
| 573 | 9753291 | In contrast, epinephrine had no effect on ERK phosphorylation or RSK2 activity, but it increased JNK activity by twofold, an effect that was inhibited by the presence of combined alpha and beta blockade. |
| 574 | 9753291 | The activity and phosphorylation of MAP kinase kinase (MKK)-4, an upstream regulator of JNK, was unchanged by epinephrine. |
| 575 | 9753291 | Insulin and epinephrine have different effects on MAP kinase signaling pathways in skeletal muscle, which may be one of the underlying molecular mechanisms through which these hormones regulate opposing metabolic functions. |
| 576 | 9753291 | Little is known about the regulation of the mitogen-activated protein (MAP) kinase signaling cascades by hormonal stimulation in vivo. |
| 577 | 9753291 | The extracellular signal-regulated kinase (ERK) and the c-jun kinase (JNK) are two MAP kinase signaling pathways that could play a role in the cellular response to hormones such as insulin and epinephrine. |
| 578 | 9753291 | We studied the effects of insulin (20 U/rat) and epinephrine (25 microg/100 g body wt) injected in vivo on ERK and JNK signaling in skeletal muscle from Sprague-Dawley rats. |
| 579 | 9753291 | Insulin significantly increased ERK phosphorylation and the activity of its downstream substrate, the p90 ribosomal S6 kinase 2 (RSK2), by 1.4-fold, but it had no effect on JNK activity. |
| 580 | 9753291 | In contrast, epinephrine had no effect on ERK phosphorylation or RSK2 activity, but it increased JNK activity by twofold, an effect that was inhibited by the presence of combined alpha and beta blockade. |
| 581 | 9753291 | The activity and phosphorylation of MAP kinase kinase (MKK)-4, an upstream regulator of JNK, was unchanged by epinephrine. |
| 582 | 9753291 | Insulin and epinephrine have different effects on MAP kinase signaling pathways in skeletal muscle, which may be one of the underlying molecular mechanisms through which these hormones regulate opposing metabolic functions. |
| 583 | 9753291 | Little is known about the regulation of the mitogen-activated protein (MAP) kinase signaling cascades by hormonal stimulation in vivo. |
| 584 | 9753291 | The extracellular signal-regulated kinase (ERK) and the c-jun kinase (JNK) are two MAP kinase signaling pathways that could play a role in the cellular response to hormones such as insulin and epinephrine. |
| 585 | 9753291 | We studied the effects of insulin (20 U/rat) and epinephrine (25 microg/100 g body wt) injected in vivo on ERK and JNK signaling in skeletal muscle from Sprague-Dawley rats. |
| 586 | 9753291 | Insulin significantly increased ERK phosphorylation and the activity of its downstream substrate, the p90 ribosomal S6 kinase 2 (RSK2), by 1.4-fold, but it had no effect on JNK activity. |
| 587 | 9753291 | In contrast, epinephrine had no effect on ERK phosphorylation or RSK2 activity, but it increased JNK activity by twofold, an effect that was inhibited by the presence of combined alpha and beta blockade. |
| 588 | 9753291 | The activity and phosphorylation of MAP kinase kinase (MKK)-4, an upstream regulator of JNK, was unchanged by epinephrine. |
| 589 | 9753291 | Insulin and epinephrine have different effects on MAP kinase signaling pathways in skeletal muscle, which may be one of the underlying molecular mechanisms through which these hormones regulate opposing metabolic functions. |
| 590 | 9753291 | Little is known about the regulation of the mitogen-activated protein (MAP) kinase signaling cascades by hormonal stimulation in vivo. |
| 591 | 9753291 | The extracellular signal-regulated kinase (ERK) and the c-jun kinase (JNK) are two MAP kinase signaling pathways that could play a role in the cellular response to hormones such as insulin and epinephrine. |
| 592 | 9753291 | We studied the effects of insulin (20 U/rat) and epinephrine (25 microg/100 g body wt) injected in vivo on ERK and JNK signaling in skeletal muscle from Sprague-Dawley rats. |
| 593 | 9753291 | Insulin significantly increased ERK phosphorylation and the activity of its downstream substrate, the p90 ribosomal S6 kinase 2 (RSK2), by 1.4-fold, but it had no effect on JNK activity. |
| 594 | 9753291 | In contrast, epinephrine had no effect on ERK phosphorylation or RSK2 activity, but it increased JNK activity by twofold, an effect that was inhibited by the presence of combined alpha and beta blockade. |
| 595 | 9753291 | The activity and phosphorylation of MAP kinase kinase (MKK)-4, an upstream regulator of JNK, was unchanged by epinephrine. |
| 596 | 9753291 | Insulin and epinephrine have different effects on MAP kinase signaling pathways in skeletal muscle, which may be one of the underlying molecular mechanisms through which these hormones regulate opposing metabolic functions. |
| 597 | 9803467 | TDs act at various levels of glucose and lipid metabolism--ameliorate some defects in the signalling cascade distal to the insulin receptor and improve glucose uptake in insulin-resistant tissues via increased expression of glucose transporters GLUT1 and GLUT4. |
| 598 | 9803467 | TDs bind to peroxisome proliferator activating receptors gamma (PPAR gamma), members of the steroid/thyroid hormone nuclear receptor superfamily of transcription factors involved in adipocyte differentiation and glucose and lipid homeostasis. |
| 599 | 9803467 | Activation of PPAR gamma results in the expression of adipocyte-specific genes and differentiation of various cell types in mature adipocytes capable of active glucose uptake and energy storage in the form of lipids. |
| 600 | 9803467 | These effects are most likely also mediated by stimulation of PPAR gamma. |
| 601 | 9803467 | In mature adipocytes, PPAR gamma stimulation inhibits stearoyl-CoA desaturase 1 (SCD1) enzyme activity resulting in a change of cell membrane fatty acid composition. |
| 602 | 9803467 | A key role of TDs effects in vascular remodelling is played by inhibition of the mitogen-activated protein (MAP) kinase pathway. |
| 603 | 9803467 | A recently reported link between MAP kinase signalling pathway and PPAR gamma |
| 604 | 9803467 | TDs act at various levels of glucose and lipid metabolism--ameliorate some defects in the signalling cascade distal to the insulin receptor and improve glucose uptake in insulin-resistant tissues via increased expression of glucose transporters GLUT1 and GLUT4. |
| 605 | 9803467 | TDs bind to peroxisome proliferator activating receptors gamma (PPAR gamma), members of the steroid/thyroid hormone nuclear receptor superfamily of transcription factors involved in adipocyte differentiation and glucose and lipid homeostasis. |
| 606 | 9803467 | Activation of PPAR gamma results in the expression of adipocyte-specific genes and differentiation of various cell types in mature adipocytes capable of active glucose uptake and energy storage in the form of lipids. |
| 607 | 9803467 | These effects are most likely also mediated by stimulation of PPAR gamma. |
| 608 | 9803467 | In mature adipocytes, PPAR gamma stimulation inhibits stearoyl-CoA desaturase 1 (SCD1) enzyme activity resulting in a change of cell membrane fatty acid composition. |
| 609 | 9803467 | A key role of TDs effects in vascular remodelling is played by inhibition of the mitogen-activated protein (MAP) kinase pathway. |
| 610 | 9803467 | A recently reported link between MAP kinase signalling pathway and PPAR gamma |
| 611 | 9814671 | Since it has been reported that such factors involved in coagulation/fibrinolysis as tissue factor, tissue factor pathway inhibitor (TFPI), thrombin receptor and urokinase receptor are also localized in the caveolae, this membrane structure may act as a special component to regulate coagulation/fibrinolysis on the endothelial membrane surface. |
| 612 | 9814671 | Next we demonstrate the signaling pathway of the thrombin receptor. |
| 613 | 9814671 | We have identified that the signal from the thrombin receptor activates NF-kappaB through the activation of protein C kinase, tyrosine kinase and MAP kinase, and results in proliferation of the cells. |
| 614 | 9833175 | Accordingly, obesity can be associated with an increased activity of the sympathetic nervous system, elevated plasma levels of the vasoconstrictor endothelin-1, and decreased insulin-induced endothelium-dependent vasodilation. |
| 615 | 9833175 | The results show that insulin can affect the expression rate of various genes, e.g. involved in cholesterol and fatty acid metabolism, by modulating the activity of transcription factors coupled to the MAP kinase cascade and that a genetic postreceptor defect in these intracellular signaling pathways might have a pleiotropic effect on cell metabolism and clinical phenotype. |
| 616 | 9845075 | PPAR-gamma (for peroxisome proliferator-activated receptor) is a nuclear hormone receptor that mediates adipocyte differentiation and modulates insulin sensitivity, cell proliferation and inflammatory processes. |
| 617 | 9845075 | Modification of the A/B domain, for example by physiological phosphorylation by MAP kinase, reduces ligand-binding affinity, thus negatively regulating the transcriptional and biological functions of PPAR-gamma. |
| 618 | 9846883 | AGE-binding receptors are: scavenger receptors types I and II, the receptor for advanced glycation endproducts (RAGE), oligosaccharyl transferase-48 (OST-48, AGE-R1), 80K-H phosphoprotein (AGE-R2) and galectin-3 (AGE-R3). |
| 619 | 9846883 | Scavenger receptors have only been shown to bind proteins modified by AGE to a much higher extent than found in vivo. 80K-H phosphoprotein is involved in FGFR3 signal transduction to MAP kinase, and may be involved in AGE-receptor signal transduction. |
| 620 | 9932214 | The binding of insulin to its receptor induces autophosphorylation of the receptor on tyrosine residues and thereby stimulates its tyrosine kinase activity towards intracellular substrates such as Shc or IRS1. |
| 621 | 9932214 | Tyrosine phosphorylation of IRSs and Shc by the insulin receptor permits the activation of two major signalling pathways, the MAP kinase pathway and the Pl 3-kinase pathway. |
| 622 | 9932214 | The MAP kinase pathway does not appear to play a significant role in the transmission of the metabolic effects of insulin. |
| 623 | 9932214 | The binding of insulin to its receptor induces autophosphorylation of the receptor on tyrosine residues and thereby stimulates its tyrosine kinase activity towards intracellular substrates such as Shc or IRS1. |
| 624 | 9932214 | Tyrosine phosphorylation of IRSs and Shc by the insulin receptor permits the activation of two major signalling pathways, the MAP kinase pathway and the Pl 3-kinase pathway. |
| 625 | 9932214 | The MAP kinase pathway does not appear to play a significant role in the transmission of the metabolic effects of insulin. |
| 626 | 10078574 | Hyperglycemia inhibits insulin activation of Akt/protein kinase B but not phosphatidylinositol 3-kinase in rat skeletal muscle. |
| 627 | 10078574 | Studies of insulin signaling in the latter muscles revealed that activation of Akt/protein kinase B (PKB) was diminished by 60%, compared with that of muscles preincubated in a glucose-free medium; whereas activation of phosphatidylinositol (PI) 3-kinase, an upstream regulator of Akt/PKB in the insulin-signaling cascade, and of mitogen-activated protein (MAP) kinase, a parallel signal, was unaffected. |
| 628 | 10078574 | They suggest that impairment of insulin action in these muscles is related to inhibition of Akt/PKB by events that do not affect PI 3-kinase. |
| 629 | 10194520 | Leptin signalling in pancreatic islets and clonal insulin-secreting cells. |
| 630 | 10194520 | In addition to its anorectic and thermogenic central actions, leptin is known to act on peripheral tissues, including the pancreatic beta-cell where it inhibits insulin secretion and reduces insulin transcript levels. |
| 631 | 10194520 | In the present study, we show that leptin activates a signal transducer and activator of transcription (STAT)3 signalling mechanism in pancreatic islets and in a rat model of the pancreatic beta-cell, RINm5F. |
| 632 | 10194520 | Leptin induced DNA binding to a STAT consensus oligonucleotide and resulted in transcriptional activation from STAT reporter constructs in a manner consistent with STAT3 activation. |
| 633 | 10194520 | Conditions that mimic increased metabolic activity resulted in attenuation of leptin-mediated STAT DNA binding but had no significant effect on STAT3 tyrosine phosphorylation in RINm5F cells. |
| 634 | 10194520 | In addition, leptin activated the mitogen activated protein (MAP) kinase pathway in RINm5F cells. |
| 635 | 10318852 | Membrane-targeted phosphatidylinositol 3-kinase mimics insulin actions and induces a state of cellular insulin resistance. |
| 636 | 10318852 | Even at this submaximal PI 3-kinase activity, p110(CAAX) fully stimulated p70 S6 kinase, Akt, 2-deoxyglucose uptake, and Ras, whereas, p110(WT) had little or no effect on these downstream effects. |
| 637 | 10318852 | Interestingly p110(CAAX) did not activate MAP kinase, despite its stimulation of p21(ras). |
| 638 | 10318852 | Surprisingly, p110(CAAX) did not increase basal glycogen synthase activity, and inhibited insulin stimulated activity, indicative of cellular resistance to this action of insulin. p110(CAAX) also inhibited insulin stimulated, but not platelet-derived growth factor-stimulated mitogen-activated protein kinase phosphorylation, demonstrating that the p110(CAAX) induced inhibition of mitogen-activated protein kinase and insulin signaling is specific, and not due to some toxic or nonspecific effect on the cells. |
| 639 | 10318852 | Moreover, p110(CAAX) stimulated IRS-1 Ser/Thr phosphorylation, and inhibited IRS-1 associated PI 3-kinase activity, without affecting insulin receptor tyrosine phosphorylation, suggesting that it may play an important role as a negative regulator for insulin signaling. |
| 640 | 10320053 | It has been known for some time that down-regulation and reduced kinase activity of the insulin receptor play a role in insulin resistance; however, it has recently emerged that defects in the intracellular responses to insulin are also very important. |
| 641 | 10320053 | We found that the insulin-stimulated activation of MAP kinase was defective in obese, insulin-resistant mice. |
| 642 | 10320053 | Similarly, we investigated insulin-stimulated PI3-kinase activation in the isolated soleus muscle of lean and obese mice, and found a marked reduction in the PI3-kinase activation of obese animals. |
| 643 | 10320053 | The magnitude of the effect was greater than the reduction in insulin receptor activation, suggesting that impairment of PI3-kinase activation is a very important element in the development of insulin resistance in obese mice. |
| 644 | 10320053 | In keeping with this, we found that the defect in PI3-kinase activation developed in young obese mice before the emergence of overt insulin resistance. |
| 645 | 10320053 | In adipocytes from young obese mice in which insulin resistance had not yet developed, we found that there were already marked defects in IRS-1 tyrosine phosphorylation. |
| 646 | 10320053 | Such a process could contribute to the defective IRS-1 tyrosine phosphorylation in insulin-resistant animals. |
| 647 | 10320053 | We found that brief exposure of 3T3-L1 adipocytes to platelet-derived growth factor led to IRS-1 serine/threonine phosphorylation through a PI3-kinase-dependent pathway, and that this prevented phosphorylation of the tyrosine residues of IRS-1. |
| 648 | 10320053 | Such a mechanism, induced by growth factors, TNF-alpha or some other agent, may play an important role in the development of insulin resistance in obese mice. |
| 649 | 10329981 | Differential regulation of MAP kinase, p70(S6K), and Akt by contraction and insulin in rat skeletal muscle. |
| 650 | 10329981 | To study the effects of contractile activity on mitogen-activated protein kinase (MAP kinase), p70 S6 kinase (p70(S6K)), and Akt kinase signaling in rat skeletal muscle, hindlimb muscles were contracted by electrical stimulation of the sciatic nerve for periods of 15 s to 60 min. |
| 651 | 10329981 | Contraction resulted in a rapid and transient activation of Raf-1 and MAP kinase kinase 1, a rapid and more sustained activation of MAP kinase and the 90-kDa ribosomal S6 kinase 2, and a dramatic increase in c-fos mRNA expression. |
| 652 | 10329981 | Contraction also resulted in an apparent increase in the association of Raf-1 with p21Ras, although stimulation of MAP kinase signaling occurred independent of Shc, IRS1, and IRS2 tyrosine phosphorylation or the formation of Shc/Grb2 or IRS1/Grb2 complexes. |
| 653 | 10329981 | Insulin was considerably less effective than contraction in stimulating the MAP kinase pathway. |
| 654 | 10329981 | However, insulin, but not contraction, increased p70(S6K) and Akt activities in the muscle. |
| 655 | 10329981 | These results demonstrate that contraction-induced activation of the MAP kinase pathway is independent of proximal steps in insulin and/or growth factor-mediated signaling, and that contraction and insulin have discordant effects with respect to the activation of the MAP kinase pathway vs. p70(S6K) and Akt. |
| 656 | 10329981 | Of the numerous stimulators of MAP kinase in skeletal muscle, contractile activity emerges as a potent and physiologically relevant activator of MAP kinase signaling, and thus activation of this pathway is likely to be an important molecular mechanism by which skeletal muscle cells transduce mechanical and/or biochemical signals into downstream biological responses. |
| 657 | 10329981 | Differential regulation of MAP kinase, p70(S6K), and Akt by contraction and insulin in rat skeletal muscle. |
| 658 | 10329981 | To study the effects of contractile activity on mitogen-activated protein kinase (MAP kinase), p70 S6 kinase (p70(S6K)), and Akt kinase signaling in rat skeletal muscle, hindlimb muscles were contracted by electrical stimulation of the sciatic nerve for periods of 15 s to 60 min. |
| 659 | 10329981 | Contraction resulted in a rapid and transient activation of Raf-1 and MAP kinase kinase 1, a rapid and more sustained activation of MAP kinase and the 90-kDa ribosomal S6 kinase 2, and a dramatic increase in c-fos mRNA expression. |
| 660 | 10329981 | Contraction also resulted in an apparent increase in the association of Raf-1 with p21Ras, although stimulation of MAP kinase signaling occurred independent of Shc, IRS1, and IRS2 tyrosine phosphorylation or the formation of Shc/Grb2 or IRS1/Grb2 complexes. |
| 661 | 10329981 | Insulin was considerably less effective than contraction in stimulating the MAP kinase pathway. |
| 662 | 10329981 | However, insulin, but not contraction, increased p70(S6K) and Akt activities in the muscle. |
| 663 | 10329981 | These results demonstrate that contraction-induced activation of the MAP kinase pathway is independent of proximal steps in insulin and/or growth factor-mediated signaling, and that contraction and insulin have discordant effects with respect to the activation of the MAP kinase pathway vs. p70(S6K) and Akt. |
| 664 | 10329981 | Of the numerous stimulators of MAP kinase in skeletal muscle, contractile activity emerges as a potent and physiologically relevant activator of MAP kinase signaling, and thus activation of this pathway is likely to be an important molecular mechanism by which skeletal muscle cells transduce mechanical and/or biochemical signals into downstream biological responses. |
| 665 | 10329981 | Differential regulation of MAP kinase, p70(S6K), and Akt by contraction and insulin in rat skeletal muscle. |
| 666 | 10329981 | To study the effects of contractile activity on mitogen-activated protein kinase (MAP kinase), p70 S6 kinase (p70(S6K)), and Akt kinase signaling in rat skeletal muscle, hindlimb muscles were contracted by electrical stimulation of the sciatic nerve for periods of 15 s to 60 min. |
| 667 | 10329981 | Contraction resulted in a rapid and transient activation of Raf-1 and MAP kinase kinase 1, a rapid and more sustained activation of MAP kinase and the 90-kDa ribosomal S6 kinase 2, and a dramatic increase in c-fos mRNA expression. |
| 668 | 10329981 | Contraction also resulted in an apparent increase in the association of Raf-1 with p21Ras, although stimulation of MAP kinase signaling occurred independent of Shc, IRS1, and IRS2 tyrosine phosphorylation or the formation of Shc/Grb2 or IRS1/Grb2 complexes. |
| 669 | 10329981 | Insulin was considerably less effective than contraction in stimulating the MAP kinase pathway. |
| 670 | 10329981 | However, insulin, but not contraction, increased p70(S6K) and Akt activities in the muscle. |
| 671 | 10329981 | These results demonstrate that contraction-induced activation of the MAP kinase pathway is independent of proximal steps in insulin and/or growth factor-mediated signaling, and that contraction and insulin have discordant effects with respect to the activation of the MAP kinase pathway vs. p70(S6K) and Akt. |
| 672 | 10329981 | Of the numerous stimulators of MAP kinase in skeletal muscle, contractile activity emerges as a potent and physiologically relevant activator of MAP kinase signaling, and thus activation of this pathway is likely to be an important molecular mechanism by which skeletal muscle cells transduce mechanical and/or biochemical signals into downstream biological responses. |
| 673 | 10329981 | Differential regulation of MAP kinase, p70(S6K), and Akt by contraction and insulin in rat skeletal muscle. |
| 674 | 10329981 | To study the effects of contractile activity on mitogen-activated protein kinase (MAP kinase), p70 S6 kinase (p70(S6K)), and Akt kinase signaling in rat skeletal muscle, hindlimb muscles were contracted by electrical stimulation of the sciatic nerve for periods of 15 s to 60 min. |
| 675 | 10329981 | Contraction resulted in a rapid and transient activation of Raf-1 and MAP kinase kinase 1, a rapid and more sustained activation of MAP kinase and the 90-kDa ribosomal S6 kinase 2, and a dramatic increase in c-fos mRNA expression. |
| 676 | 10329981 | Contraction also resulted in an apparent increase in the association of Raf-1 with p21Ras, although stimulation of MAP kinase signaling occurred independent of Shc, IRS1, and IRS2 tyrosine phosphorylation or the formation of Shc/Grb2 or IRS1/Grb2 complexes. |
| 677 | 10329981 | Insulin was considerably less effective than contraction in stimulating the MAP kinase pathway. |
| 678 | 10329981 | However, insulin, but not contraction, increased p70(S6K) and Akt activities in the muscle. |
| 679 | 10329981 | These results demonstrate that contraction-induced activation of the MAP kinase pathway is independent of proximal steps in insulin and/or growth factor-mediated signaling, and that contraction and insulin have discordant effects with respect to the activation of the MAP kinase pathway vs. p70(S6K) and Akt. |
| 680 | 10329981 | Of the numerous stimulators of MAP kinase in skeletal muscle, contractile activity emerges as a potent and physiologically relevant activator of MAP kinase signaling, and thus activation of this pathway is likely to be an important molecular mechanism by which skeletal muscle cells transduce mechanical and/or biochemical signals into downstream biological responses. |
| 681 | 10329981 | Differential regulation of MAP kinase, p70(S6K), and Akt by contraction and insulin in rat skeletal muscle. |
| 682 | 10329981 | To study the effects of contractile activity on mitogen-activated protein kinase (MAP kinase), p70 S6 kinase (p70(S6K)), and Akt kinase signaling in rat skeletal muscle, hindlimb muscles were contracted by electrical stimulation of the sciatic nerve for periods of 15 s to 60 min. |
| 683 | 10329981 | Contraction resulted in a rapid and transient activation of Raf-1 and MAP kinase kinase 1, a rapid and more sustained activation of MAP kinase and the 90-kDa ribosomal S6 kinase 2, and a dramatic increase in c-fos mRNA expression. |
| 684 | 10329981 | Contraction also resulted in an apparent increase in the association of Raf-1 with p21Ras, although stimulation of MAP kinase signaling occurred independent of Shc, IRS1, and IRS2 tyrosine phosphorylation or the formation of Shc/Grb2 or IRS1/Grb2 complexes. |
| 685 | 10329981 | Insulin was considerably less effective than contraction in stimulating the MAP kinase pathway. |
| 686 | 10329981 | However, insulin, but not contraction, increased p70(S6K) and Akt activities in the muscle. |
| 687 | 10329981 | These results demonstrate that contraction-induced activation of the MAP kinase pathway is independent of proximal steps in insulin and/or growth factor-mediated signaling, and that contraction and insulin have discordant effects with respect to the activation of the MAP kinase pathway vs. p70(S6K) and Akt. |
| 688 | 10329981 | Of the numerous stimulators of MAP kinase in skeletal muscle, contractile activity emerges as a potent and physiologically relevant activator of MAP kinase signaling, and thus activation of this pathway is likely to be an important molecular mechanism by which skeletal muscle cells transduce mechanical and/or biochemical signals into downstream biological responses. |
| 689 | 10329981 | Differential regulation of MAP kinase, p70(S6K), and Akt by contraction and insulin in rat skeletal muscle. |
| 690 | 10329981 | To study the effects of contractile activity on mitogen-activated protein kinase (MAP kinase), p70 S6 kinase (p70(S6K)), and Akt kinase signaling in rat skeletal muscle, hindlimb muscles were contracted by electrical stimulation of the sciatic nerve for periods of 15 s to 60 min. |
| 691 | 10329981 | Contraction resulted in a rapid and transient activation of Raf-1 and MAP kinase kinase 1, a rapid and more sustained activation of MAP kinase and the 90-kDa ribosomal S6 kinase 2, and a dramatic increase in c-fos mRNA expression. |
| 692 | 10329981 | Contraction also resulted in an apparent increase in the association of Raf-1 with p21Ras, although stimulation of MAP kinase signaling occurred independent of Shc, IRS1, and IRS2 tyrosine phosphorylation or the formation of Shc/Grb2 or IRS1/Grb2 complexes. |
| 693 | 10329981 | Insulin was considerably less effective than contraction in stimulating the MAP kinase pathway. |
| 694 | 10329981 | However, insulin, but not contraction, increased p70(S6K) and Akt activities in the muscle. |
| 695 | 10329981 | These results demonstrate that contraction-induced activation of the MAP kinase pathway is independent of proximal steps in insulin and/or growth factor-mediated signaling, and that contraction and insulin have discordant effects with respect to the activation of the MAP kinase pathway vs. p70(S6K) and Akt. |
| 696 | 10329981 | Of the numerous stimulators of MAP kinase in skeletal muscle, contractile activity emerges as a potent and physiologically relevant activator of MAP kinase signaling, and thus activation of this pathway is likely to be an important molecular mechanism by which skeletal muscle cells transduce mechanical and/or biochemical signals into downstream biological responses. |
| 697 | 10329981 | Differential regulation of MAP kinase, p70(S6K), and Akt by contraction and insulin in rat skeletal muscle. |
| 698 | 10329981 | To study the effects of contractile activity on mitogen-activated protein kinase (MAP kinase), p70 S6 kinase (p70(S6K)), and Akt kinase signaling in rat skeletal muscle, hindlimb muscles were contracted by electrical stimulation of the sciatic nerve for periods of 15 s to 60 min. |
| 699 | 10329981 | Contraction resulted in a rapid and transient activation of Raf-1 and MAP kinase kinase 1, a rapid and more sustained activation of MAP kinase and the 90-kDa ribosomal S6 kinase 2, and a dramatic increase in c-fos mRNA expression. |
| 700 | 10329981 | Contraction also resulted in an apparent increase in the association of Raf-1 with p21Ras, although stimulation of MAP kinase signaling occurred independent of Shc, IRS1, and IRS2 tyrosine phosphorylation or the formation of Shc/Grb2 or IRS1/Grb2 complexes. |
| 701 | 10329981 | Insulin was considerably less effective than contraction in stimulating the MAP kinase pathway. |
| 702 | 10329981 | However, insulin, but not contraction, increased p70(S6K) and Akt activities in the muscle. |
| 703 | 10329981 | These results demonstrate that contraction-induced activation of the MAP kinase pathway is independent of proximal steps in insulin and/or growth factor-mediated signaling, and that contraction and insulin have discordant effects with respect to the activation of the MAP kinase pathway vs. p70(S6K) and Akt. |
| 704 | 10329981 | Of the numerous stimulators of MAP kinase in skeletal muscle, contractile activity emerges as a potent and physiologically relevant activator of MAP kinase signaling, and thus activation of this pathway is likely to be an important molecular mechanism by which skeletal muscle cells transduce mechanical and/or biochemical signals into downstream biological responses. |
| 705 | 10397676 | Oxidized LDL-containing immune complexes induce Fc gamma receptor I-mediated mitogen-activated protein kinase activation in THP-1 macrophages. |
| 706 | 10397676 | In this study, we determined whether engagement of FcgammaR by oxLDL-ICs leads to activation of mitogen-activated protein (MAP) kinase pathway, a signaling cascade serving many important functions, including the regulation of gene expression, in THP-1 macrophage-like cells. |
| 707 | 10397676 | Our results from immunoblotting, using specific anti-phosphorylated MAP kinase antibodies, showed that oxLDL-ICs induced extracellular signal regulated kinase 2 (ERK2) MAP kinase phosphorylation in THP-1 macrophage-like cells in time- and dose-dependent manners. |
| 708 | 10397676 | Moreover, our data showed that oxLDL-IC induction of MAP kinase was prevented by human monomeric IgG1, suggesting that the specific engagement of type I FcgammaR by oxLDL-IC is responsible for the MAP kinase activation. |
| 709 | 10397676 | Finally, we showed that human anti-oxLDL autoantibody-containing immune complexes immobilized on type I collagen induced MAP kinase activation in THP-1 cells. |
| 710 | 10397676 | Oxidized LDL-containing immune complexes induce Fc gamma receptor I-mediated mitogen-activated protein kinase activation in THP-1 macrophages. |
| 711 | 10397676 | In this study, we determined whether engagement of FcgammaR by oxLDL-ICs leads to activation of mitogen-activated protein (MAP) kinase pathway, a signaling cascade serving many important functions, including the regulation of gene expression, in THP-1 macrophage-like cells. |
| 712 | 10397676 | Our results from immunoblotting, using specific anti-phosphorylated MAP kinase antibodies, showed that oxLDL-ICs induced extracellular signal regulated kinase 2 (ERK2) MAP kinase phosphorylation in THP-1 macrophage-like cells in time- and dose-dependent manners. |
| 713 | 10397676 | Moreover, our data showed that oxLDL-IC induction of MAP kinase was prevented by human monomeric IgG1, suggesting that the specific engagement of type I FcgammaR by oxLDL-IC is responsible for the MAP kinase activation. |
| 714 | 10397676 | Finally, we showed that human anti-oxLDL autoantibody-containing immune complexes immobilized on type I collagen induced MAP kinase activation in THP-1 cells. |
| 715 | 10397676 | Oxidized LDL-containing immune complexes induce Fc gamma receptor I-mediated mitogen-activated protein kinase activation in THP-1 macrophages. |
| 716 | 10397676 | In this study, we determined whether engagement of FcgammaR by oxLDL-ICs leads to activation of mitogen-activated protein (MAP) kinase pathway, a signaling cascade serving many important functions, including the regulation of gene expression, in THP-1 macrophage-like cells. |
| 717 | 10397676 | Our results from immunoblotting, using specific anti-phosphorylated MAP kinase antibodies, showed that oxLDL-ICs induced extracellular signal regulated kinase 2 (ERK2) MAP kinase phosphorylation in THP-1 macrophage-like cells in time- and dose-dependent manners. |
| 718 | 10397676 | Moreover, our data showed that oxLDL-IC induction of MAP kinase was prevented by human monomeric IgG1, suggesting that the specific engagement of type I FcgammaR by oxLDL-IC is responsible for the MAP kinase activation. |
| 719 | 10397676 | Finally, we showed that human anti-oxLDL autoantibody-containing immune complexes immobilized on type I collagen induced MAP kinase activation in THP-1 cells. |
| 720 | 10397676 | Oxidized LDL-containing immune complexes induce Fc gamma receptor I-mediated mitogen-activated protein kinase activation in THP-1 macrophages. |
| 721 | 10397676 | In this study, we determined whether engagement of FcgammaR by oxLDL-ICs leads to activation of mitogen-activated protein (MAP) kinase pathway, a signaling cascade serving many important functions, including the regulation of gene expression, in THP-1 macrophage-like cells. |
| 722 | 10397676 | Our results from immunoblotting, using specific anti-phosphorylated MAP kinase antibodies, showed that oxLDL-ICs induced extracellular signal regulated kinase 2 (ERK2) MAP kinase phosphorylation in THP-1 macrophage-like cells in time- and dose-dependent manners. |
| 723 | 10397676 | Moreover, our data showed that oxLDL-IC induction of MAP kinase was prevented by human monomeric IgG1, suggesting that the specific engagement of type I FcgammaR by oxLDL-IC is responsible for the MAP kinase activation. |
| 724 | 10397676 | Finally, we showed that human anti-oxLDL autoantibody-containing immune complexes immobilized on type I collagen induced MAP kinase activation in THP-1 cells. |
| 725 | 10449437 | In this report, insulin signaling on the phosphatidylinositol 3-kinase (PI 3-kinase) and mitogen-activated protein (MAP) kinase pathways were compared in vascular tissues of lean and obese Zucker (fa/fa) rats in both ex vivo and in vivo studies. |
| 726 | 10449437 | Ex vivo, insulin-stimulated tyrosine phosphorylation of insulin receptor beta subunits (IRbeta) in the aorta and microvessels of obese rats was significantly decreased compared with lean rats, although the protein levels of IRbeta in the 2 groups were not different. |
| 727 | 10449437 | Insulin-induced tyrosine phosphorylation of insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) and their protein levels were decreased in the aorta of obese rats compared with lean rats. |
| 728 | 10449437 | The association of p85 subunit to the IRS proteins and the IRS-associated PI 3-kinase activities stimulated by insulin in the aorta of obese rats were significantly decreased compared with the lean rats. |
| 729 | 10449437 | In addition, insulin-stimulated serine phosphorylation of Akt, a downstream kinase of PI 3-kinase pathway, was also reduced significantly in isolated microvessels from obese rats compared with the lean rats. |
| 730 | 10449437 | In contrast, insulin stimulated tyrosine phosphorylation of MAP kinase (ERK-1/2) equally in isolated microvessels of lean and obese rats, although basal tyrosine phosphorylation of ERK-1/2 was higher in the obese rats. |
| 731 | 10449437 | To our knowledge, these data provided the first direct measurements of insulin signaling in the vascular tissues, and documented a selective resistance to PI 3-kinase (but not to MAP kinase pathway) in the vascular tissues of obese Zucker rats. |
| 732 | 10449437 | In this report, insulin signaling on the phosphatidylinositol 3-kinase (PI 3-kinase) and mitogen-activated protein (MAP) kinase pathways were compared in vascular tissues of lean and obese Zucker (fa/fa) rats in both ex vivo and in vivo studies. |
| 733 | 10449437 | Ex vivo, insulin-stimulated tyrosine phosphorylation of insulin receptor beta subunits (IRbeta) in the aorta and microvessels of obese rats was significantly decreased compared with lean rats, although the protein levels of IRbeta in the 2 groups were not different. |
| 734 | 10449437 | Insulin-induced tyrosine phosphorylation of insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) and their protein levels were decreased in the aorta of obese rats compared with lean rats. |
| 735 | 10449437 | The association of p85 subunit to the IRS proteins and the IRS-associated PI 3-kinase activities stimulated by insulin in the aorta of obese rats were significantly decreased compared with the lean rats. |
| 736 | 10449437 | In addition, insulin-stimulated serine phosphorylation of Akt, a downstream kinase of PI 3-kinase pathway, was also reduced significantly in isolated microvessels from obese rats compared with the lean rats. |
| 737 | 10449437 | In contrast, insulin stimulated tyrosine phosphorylation of MAP kinase (ERK-1/2) equally in isolated microvessels of lean and obese rats, although basal tyrosine phosphorylation of ERK-1/2 was higher in the obese rats. |
| 738 | 10449437 | To our knowledge, these data provided the first direct measurements of insulin signaling in the vascular tissues, and documented a selective resistance to PI 3-kinase (but not to MAP kinase pathway) in the vascular tissues of obese Zucker rats. |
| 739 | 10449437 | In this report, insulin signaling on the phosphatidylinositol 3-kinase (PI 3-kinase) and mitogen-activated protein (MAP) kinase pathways were compared in vascular tissues of lean and obese Zucker (fa/fa) rats in both ex vivo and in vivo studies. |
| 740 | 10449437 | Ex vivo, insulin-stimulated tyrosine phosphorylation of insulin receptor beta subunits (IRbeta) in the aorta and microvessels of obese rats was significantly decreased compared with lean rats, although the protein levels of IRbeta in the 2 groups were not different. |
| 741 | 10449437 | Insulin-induced tyrosine phosphorylation of insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) and their protein levels were decreased in the aorta of obese rats compared with lean rats. |
| 742 | 10449437 | The association of p85 subunit to the IRS proteins and the IRS-associated PI 3-kinase activities stimulated by insulin in the aorta of obese rats were significantly decreased compared with the lean rats. |
| 743 | 10449437 | In addition, insulin-stimulated serine phosphorylation of Akt, a downstream kinase of PI 3-kinase pathway, was also reduced significantly in isolated microvessels from obese rats compared with the lean rats. |
| 744 | 10449437 | In contrast, insulin stimulated tyrosine phosphorylation of MAP kinase (ERK-1/2) equally in isolated microvessels of lean and obese rats, although basal tyrosine phosphorylation of ERK-1/2 was higher in the obese rats. |
| 745 | 10449437 | To our knowledge, these data provided the first direct measurements of insulin signaling in the vascular tissues, and documented a selective resistance to PI 3-kinase (but not to MAP kinase pathway) in the vascular tissues of obese Zucker rats. |
| 746 | 10516100 | Physical exercise is a potent stimulator of mitogen-activated protein (MAP) kinase signaling. |
| 747 | 10516100 | Contractile activity in vitro significantly increased p44(MAPK) and p42(MAPK) phosphorylation by 2.9- and 2.4-fold, respectively. |
| 748 | 10516100 | Contraction-stimulated MAP kinase phosphorylation was not decreased in the presence of D-tubocurarine or calphostin C, suggesting that neither neurotransmitter release nor diacylglycerol-sensitive protein kinase C mediates the contraction-induced activation of this signaling cascade. |
| 749 | 10516100 | However, PD-98059, an inhibitor of MAP kinase kinase (MEK), inhibited the contraction-induced increases in MAP kinase phosphorylation. |
| 750 | 10516100 | PD-98059 did not alter contraction-induced increases in glucose uptake or glycogen synthase activity, demonstrating that MAP kinase signaling is not necessary for these important metabolic effects of contractile activity in skeletal muscle. |
| 751 | 10516100 | These data suggest that contractile activity of the skeletal muscle fibers per se, and not responses to neurotransmitter release, hormones, or other systemic factors, is responsible for the stimulation of MAP kinase signaling with physical exercise. |
| 752 | 10516100 | Physical exercise is a potent stimulator of mitogen-activated protein (MAP) kinase signaling. |
| 753 | 10516100 | Contractile activity in vitro significantly increased p44(MAPK) and p42(MAPK) phosphorylation by 2.9- and 2.4-fold, respectively. |
| 754 | 10516100 | Contraction-stimulated MAP kinase phosphorylation was not decreased in the presence of D-tubocurarine or calphostin C, suggesting that neither neurotransmitter release nor diacylglycerol-sensitive protein kinase C mediates the contraction-induced activation of this signaling cascade. |
| 755 | 10516100 | However, PD-98059, an inhibitor of MAP kinase kinase (MEK), inhibited the contraction-induced increases in MAP kinase phosphorylation. |
| 756 | 10516100 | PD-98059 did not alter contraction-induced increases in glucose uptake or glycogen synthase activity, demonstrating that MAP kinase signaling is not necessary for these important metabolic effects of contractile activity in skeletal muscle. |
| 757 | 10516100 | These data suggest that contractile activity of the skeletal muscle fibers per se, and not responses to neurotransmitter release, hormones, or other systemic factors, is responsible for the stimulation of MAP kinase signaling with physical exercise. |
| 758 | 10516100 | Physical exercise is a potent stimulator of mitogen-activated protein (MAP) kinase signaling. |
| 759 | 10516100 | Contractile activity in vitro significantly increased p44(MAPK) and p42(MAPK) phosphorylation by 2.9- and 2.4-fold, respectively. |
| 760 | 10516100 | Contraction-stimulated MAP kinase phosphorylation was not decreased in the presence of D-tubocurarine or calphostin C, suggesting that neither neurotransmitter release nor diacylglycerol-sensitive protein kinase C mediates the contraction-induced activation of this signaling cascade. |
| 761 | 10516100 | However, PD-98059, an inhibitor of MAP kinase kinase (MEK), inhibited the contraction-induced increases in MAP kinase phosphorylation. |
| 762 | 10516100 | PD-98059 did not alter contraction-induced increases in glucose uptake or glycogen synthase activity, demonstrating that MAP kinase signaling is not necessary for these important metabolic effects of contractile activity in skeletal muscle. |
| 763 | 10516100 | These data suggest that contractile activity of the skeletal muscle fibers per se, and not responses to neurotransmitter release, hormones, or other systemic factors, is responsible for the stimulation of MAP kinase signaling with physical exercise. |
| 764 | 10516100 | Physical exercise is a potent stimulator of mitogen-activated protein (MAP) kinase signaling. |
| 765 | 10516100 | Contractile activity in vitro significantly increased p44(MAPK) and p42(MAPK) phosphorylation by 2.9- and 2.4-fold, respectively. |
| 766 | 10516100 | Contraction-stimulated MAP kinase phosphorylation was not decreased in the presence of D-tubocurarine or calphostin C, suggesting that neither neurotransmitter release nor diacylglycerol-sensitive protein kinase C mediates the contraction-induced activation of this signaling cascade. |
| 767 | 10516100 | However, PD-98059, an inhibitor of MAP kinase kinase (MEK), inhibited the contraction-induced increases in MAP kinase phosphorylation. |
| 768 | 10516100 | PD-98059 did not alter contraction-induced increases in glucose uptake or glycogen synthase activity, demonstrating that MAP kinase signaling is not necessary for these important metabolic effects of contractile activity in skeletal muscle. |
| 769 | 10516100 | These data suggest that contractile activity of the skeletal muscle fibers per se, and not responses to neurotransmitter release, hormones, or other systemic factors, is responsible for the stimulation of MAP kinase signaling with physical exercise. |
| 770 | 10516100 | Physical exercise is a potent stimulator of mitogen-activated protein (MAP) kinase signaling. |
| 771 | 10516100 | Contractile activity in vitro significantly increased p44(MAPK) and p42(MAPK) phosphorylation by 2.9- and 2.4-fold, respectively. |
| 772 | 10516100 | Contraction-stimulated MAP kinase phosphorylation was not decreased in the presence of D-tubocurarine or calphostin C, suggesting that neither neurotransmitter release nor diacylglycerol-sensitive protein kinase C mediates the contraction-induced activation of this signaling cascade. |
| 773 | 10516100 | However, PD-98059, an inhibitor of MAP kinase kinase (MEK), inhibited the contraction-induced increases in MAP kinase phosphorylation. |
| 774 | 10516100 | PD-98059 did not alter contraction-induced increases in glucose uptake or glycogen synthase activity, demonstrating that MAP kinase signaling is not necessary for these important metabolic effects of contractile activity in skeletal muscle. |
| 775 | 10516100 | These data suggest that contractile activity of the skeletal muscle fibers per se, and not responses to neurotransmitter release, hormones, or other systemic factors, is responsible for the stimulation of MAP kinase signaling with physical exercise. |
| 776 | 10593880 | Furthermore, transfection of PC12 cells with core 2 GlcNAc-T also induced c-fos promoter activation, mitogen activated-protein kinase (MAPK) phosphorylation, Trk receptor glycosylation, and cell differentiation. |
| 777 | 10593880 | These results suggested a novel role for core 2 GlcNAc-T in the development of diabetic cardiomyopathy and modulation of the MAP kinase pathway in the heart. |
| 778 | 10675357 | Insulin resistance differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle. |
| 779 | 10675357 | Insulin stimulation of the phosphatidylinositol 3-kinase (PI 3-kinase) pathway, as measured by phosphorylation of the insulin receptor and IRS-1 and by IRS protein association with p85 and with PI 3-kinase, was dramatically reduced in obese nondiabetics and virtually absent in type 2 diabetic patients. |
| 780 | 10675357 | Insulin stimulation of the MAP kinase pathway was normal in obese and diabetic subjects. |
| 781 | 10675357 | Insulin stimulation of glucose-disposal correlated with association of p85 with IRS-1. |
| 782 | 10675357 | Exercise 24 hours before the euglycemic clamp increased phosphorylation of insulin receptor and IRS-1 in obese and diabetic subjects but did not increase glucose uptake or PI 3-kinase association with IRS-1 upon insulin stimulation. |
| 783 | 10675357 | Thus, insulin resistance differentially affects the PI 3-kinase and MAP kinase signaling pathways, and insulin-stimulated IRS-1-association with PI 3-kinase defines a key step in insulin resistance. |
| 784 | 10675357 | Insulin resistance differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle. |
| 785 | 10675357 | Insulin stimulation of the phosphatidylinositol 3-kinase (PI 3-kinase) pathway, as measured by phosphorylation of the insulin receptor and IRS-1 and by IRS protein association with p85 and with PI 3-kinase, was dramatically reduced in obese nondiabetics and virtually absent in type 2 diabetic patients. |
| 786 | 10675357 | Insulin stimulation of the MAP kinase pathway was normal in obese and diabetic subjects. |
| 787 | 10675357 | Insulin stimulation of glucose-disposal correlated with association of p85 with IRS-1. |
| 788 | 10675357 | Exercise 24 hours before the euglycemic clamp increased phosphorylation of insulin receptor and IRS-1 in obese and diabetic subjects but did not increase glucose uptake or PI 3-kinase association with IRS-1 upon insulin stimulation. |
| 789 | 10675357 | Thus, insulin resistance differentially affects the PI 3-kinase and MAP kinase signaling pathways, and insulin-stimulated IRS-1-association with PI 3-kinase defines a key step in insulin resistance. |
| 790 | 10675357 | Insulin resistance differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle. |
| 791 | 10675357 | Insulin stimulation of the phosphatidylinositol 3-kinase (PI 3-kinase) pathway, as measured by phosphorylation of the insulin receptor and IRS-1 and by IRS protein association with p85 and with PI 3-kinase, was dramatically reduced in obese nondiabetics and virtually absent in type 2 diabetic patients. |
| 792 | 10675357 | Insulin stimulation of the MAP kinase pathway was normal in obese and diabetic subjects. |
| 793 | 10675357 | Insulin stimulation of glucose-disposal correlated with association of p85 with IRS-1. |
| 794 | 10675357 | Exercise 24 hours before the euglycemic clamp increased phosphorylation of insulin receptor and IRS-1 in obese and diabetic subjects but did not increase glucose uptake or PI 3-kinase association with IRS-1 upon insulin stimulation. |
| 795 | 10675357 | Thus, insulin resistance differentially affects the PI 3-kinase and MAP kinase signaling pathways, and insulin-stimulated IRS-1-association with PI 3-kinase defines a key step in insulin resistance. |
| 796 | 10707556 | The insulin-activated pathway is the phosphatidylinositol 3-kinase pathway in the endothelial cells and MAP kinase pathway in the VSMC. |
| 797 | 10751417 | Overexpression of protein-tyrosine phosphatase-1B in adipocytes inhibits insulin-stimulated phosphoinositide 3-kinase activity without altering glucose transport or Akt/Protein kinase B activation. |
| 798 | 10751417 | Previous studies suggested that protein-tyrosine phosphatase 1B (PTP1B) antagonizes insulin action by catalyzing dephosphorylation of the insulin receptor (IR) and/or other key proteins in the insulin signaling pathway. |
| 799 | 10751417 | In adipose tissue and muscle of obese humans and rodents, PTP1B expression is increased, which led to the hypothesis that PTP1B plays a role in the pathogenesis of insulin resistance. |
| 800 | 10751417 | Consistent with this, mice in which the PTP1B gene was disrupted exhibit increased insulin sensitivity. |
| 801 | 10751417 | To test whether increased expression of PTP1B in an insulin-sensitive cell type could contribute to insulin resistance, we overexpressed wild-type PTP1B in 3T3L1 adipocytes using adenovirus-mediated gene delivery. |
| 802 | 10751417 | Compared with control cells, cells expressing high levels of PTP1B showed a 50-60% decrease in maximally insulin-stimulated tyrosyl phosphorylation of IR and insulin receptor substrate-1 (IRS-1) and phosphoinositide 3-kinase (PI3K) activity associated with IRS-1 or with phosphotyrosine. |
| 803 | 10751417 | Phosphorylation of p42 and p44 MAP kinase (MAPK) was reduced approximately 32%. |
| 804 | 10751417 | Overexpression of PTP1B had no effect on basal, submaximally or maximally (100 nm) insulin-stimulated glucose transport or on the EC(50) for transport. |
| 805 | 10751417 | Our results suggest that: 1) insulin stimulation of glucose transport in adipocytes requires </=45% of maximal tyrosyl phosphorylation of IR or IRS-1 and <50% of maximal activation of PI3K, 2) a novel PI3K-independent pathway may play a role in insulin-induced glucose transport in adipocytes, and 3) overexpression of PTP1B alone in adipocytes does not impair glucose transport. |
| 806 | 10773230 | AII mediates cardiac myocyte hypertrophy directly via induction of immediate early genes through a MAP kinase dependent pathway. |
| 807 | 10847579 | Insulin and the beta3-adrenoceptor differentially regulate uncoupling protein-1 expression. |
| 808 | 10847579 | Beta3-adrenergic stimulation also activated mitogen-activated protein (MAP) kinase by 3.5-fold and caused a decrease in basal phosphoinositide (PI) 3-kinase activity detected in p110gamma- and Gbeta-subunit-immunoprecipitates in a time-dependent manner, whereas insulin stimulated p110alpha- and phosphotyrosine-associated PI 3-kinase activity. |
| 809 | 10847579 | Inhibition of MAP kinase or PI 3-kinase potentiated the beta3-adrenergic effect on UCP-1 expression, both alone and in the presence of insulin. |
| 810 | 10847579 | Thus, insulin inhibits beta3-adrenergic stimulation of UCP-1, and both MAP kinase and PI 3-kinase are negative regulatory elements in the beta3-adrenergic control of UCP-1 expression. |
| 811 | 10847579 | Cross-talk between the adrenergic and insulin signaling systems and impaired regulation of UCP-1 might contribute to the development of a reduced energy balance, resulting in obesity and insulin resistance. |
| 812 | 10847579 | Insulin and the beta3-adrenoceptor differentially regulate uncoupling protein-1 expression. |
| 813 | 10847579 | Beta3-adrenergic stimulation also activated mitogen-activated protein (MAP) kinase by 3.5-fold and caused a decrease in basal phosphoinositide (PI) 3-kinase activity detected in p110gamma- and Gbeta-subunit-immunoprecipitates in a time-dependent manner, whereas insulin stimulated p110alpha- and phosphotyrosine-associated PI 3-kinase activity. |
| 814 | 10847579 | Inhibition of MAP kinase or PI 3-kinase potentiated the beta3-adrenergic effect on UCP-1 expression, both alone and in the presence of insulin. |
| 815 | 10847579 | Thus, insulin inhibits beta3-adrenergic stimulation of UCP-1, and both MAP kinase and PI 3-kinase are negative regulatory elements in the beta3-adrenergic control of UCP-1 expression. |
| 816 | 10847579 | Cross-talk between the adrenergic and insulin signaling systems and impaired regulation of UCP-1 might contribute to the development of a reduced energy balance, resulting in obesity and insulin resistance. |
| 817 | 10847579 | Insulin and the beta3-adrenoceptor differentially regulate uncoupling protein-1 expression. |
| 818 | 10847579 | Beta3-adrenergic stimulation also activated mitogen-activated protein (MAP) kinase by 3.5-fold and caused a decrease in basal phosphoinositide (PI) 3-kinase activity detected in p110gamma- and Gbeta-subunit-immunoprecipitates in a time-dependent manner, whereas insulin stimulated p110alpha- and phosphotyrosine-associated PI 3-kinase activity. |
| 819 | 10847579 | Inhibition of MAP kinase or PI 3-kinase potentiated the beta3-adrenergic effect on UCP-1 expression, both alone and in the presence of insulin. |
| 820 | 10847579 | Thus, insulin inhibits beta3-adrenergic stimulation of UCP-1, and both MAP kinase and PI 3-kinase are negative regulatory elements in the beta3-adrenergic control of UCP-1 expression. |
| 821 | 10847579 | Cross-talk between the adrenergic and insulin signaling systems and impaired regulation of UCP-1 might contribute to the development of a reduced energy balance, resulting in obesity and insulin resistance. |
| 822 | 10868945 | Insulin-stimulated (0.6-60 nmol/l) tyrosine phosphorylation of the insulin receptor beta-subunit, mitogen-activated protein (MAP) kinase phosphorylation, and glycogen synthase activity were not altered in type 2 diabetic subjects. |
| 823 | 10868945 | In contrast, insulin-stimulated tyrosine phosphorylation of IRS-1 and anti-phosphotyrosine-associated PI 3-kinase activity were reduced 40-55% in type 2 diabetic subjects at high insulin concentrations (2.4 and 60 nmol/l, respectively). |
| 824 | 10868945 | Aberrant protein expression cannot account for these insulin-signaling defects because expression of insulin receptor, IRS-1, IRS-2, MAP kinase, or glycogen synthase was similar between type 2 diabetic and control subjects. |
| 825 | 10868945 | In skeletal muscle from type 2 diabetic subjects, IRS-1 phosphorylation, PI 3-kinase activity, and glucose transport activity were impaired, whereas insulin receptor tyrosine phosphorylation, MAP kinase phosphorylation, and glycogen synthase activity were normal. |
| 826 | 10868945 | Insulin-stimulated (0.6-60 nmol/l) tyrosine phosphorylation of the insulin receptor beta-subunit, mitogen-activated protein (MAP) kinase phosphorylation, and glycogen synthase activity were not altered in type 2 diabetic subjects. |
| 827 | 10868945 | In contrast, insulin-stimulated tyrosine phosphorylation of IRS-1 and anti-phosphotyrosine-associated PI 3-kinase activity were reduced 40-55% in type 2 diabetic subjects at high insulin concentrations (2.4 and 60 nmol/l, respectively). |
| 828 | 10868945 | Aberrant protein expression cannot account for these insulin-signaling defects because expression of insulin receptor, IRS-1, IRS-2, MAP kinase, or glycogen synthase was similar between type 2 diabetic and control subjects. |
| 829 | 10868945 | In skeletal muscle from type 2 diabetic subjects, IRS-1 phosphorylation, PI 3-kinase activity, and glucose transport activity were impaired, whereas insulin receptor tyrosine phosphorylation, MAP kinase phosphorylation, and glycogen synthase activity were normal. |
| 830 | 10868945 | Insulin-stimulated (0.6-60 nmol/l) tyrosine phosphorylation of the insulin receptor beta-subunit, mitogen-activated protein (MAP) kinase phosphorylation, and glycogen synthase activity were not altered in type 2 diabetic subjects. |
| 831 | 10868945 | In contrast, insulin-stimulated tyrosine phosphorylation of IRS-1 and anti-phosphotyrosine-associated PI 3-kinase activity were reduced 40-55% in type 2 diabetic subjects at high insulin concentrations (2.4 and 60 nmol/l, respectively). |
| 832 | 10868945 | Aberrant protein expression cannot account for these insulin-signaling defects because expression of insulin receptor, IRS-1, IRS-2, MAP kinase, or glycogen synthase was similar between type 2 diabetic and control subjects. |
| 833 | 10868945 | In skeletal muscle from type 2 diabetic subjects, IRS-1 phosphorylation, PI 3-kinase activity, and glucose transport activity were impaired, whereas insulin receptor tyrosine phosphorylation, MAP kinase phosphorylation, and glycogen synthase activity were normal. |
| 834 | 10871205 | Mechanical stretch-induced fibronectin and transforming growth factor-beta1 production in human mesangial cells is p38 mitogen-activated protein kinase-dependent. |
| 835 | 10871205 | Hemodynamic abnormalities are important in the pathogenesis of the excess mesangial matrix deposition of diabetic and other glomerulopathies. p38-Mitogen-activated protein (MAP) kinase, an important intracellular signaling molecule, is activated in the glomeruli of diabetic rats. |
| 836 | 10871205 | We studied, in human mesangial cells, the effect of stretch on p38 MAP kinase activation and the role of p38 MAP kinase in stretch-induced fibronectin and transforming growth factor-beta1 (TGF-beta1) accumulation. p38 MAP kinase was activated by stretch in a rapid (11-fold increase at 30 min, P < 0.001) and sustained manner (3-fold increase at 33 h, P < 0.001); this activation was mediated by protein kinase C (PKC). |
| 837 | 10871205 | Stretch-induced fibronectin and TGF-beta1 protein levels were completely abolished (100% inhibition, P < 0.001; and 92% inhibition, P < 0.01, respectively) by SB203580, a specific p38 MAP kinase inhibitor. |
| 838 | 10871205 | At 33 h, TGF-beta1 blockade did not affect stretch-induced fibronectin production, but partially prevented stretch-induced p38 MAP kinase activation (59% inhibition, P < 0.05). |
| 839 | 10871205 | TGF-beta1 induced fibronectin accumulation after 72 h of exposure via a p38 MAP kinase-dependent mechanism (30% increase over control, P < 0.01). |
| 840 | 10871205 | In human mesangial cells, stretch activates, via a PKC-dependent mechanism, p38 MAP kinase, which independently induces TGF-beta1 and fibronectin. |
| 841 | 10871205 | In turn, TGF-beta1 contributes to maintaining late p38 MAP kinase activation, which perpetuates fibronectin accumulation. |
| 842 | 10909971 | Activating transcription factor-2 is a positive regulator in CaM kinase IV-induced human insulin gene expression. |
| 843 | 10909971 | The activity of the transcription factor activating transcription factor-2 (ATF-2), which binds to the cAMP responsive elements of the human insulin gene, was enhanced by Ca2+/calmodulin-dependent protein kinase IV (CaMKIV). |
| 844 | 10909971 | CaMKIV-induced ATF-2 transcriptional activity was not altered by activation of cJun NH2-terminal protein kinase (JNK) or p38 mitogen-activated protein (MAP) kinase. |
| 845 | 10909971 | Furthermore, when transfected into rat primary cultured islets, ATF-2 enhanced glucose-induced insulin promoter activity, whereas cAMP response element-binding protein (CREB) repressed it. |
| 846 | 10909971 | These results suggest a mechanism in which ATF-2 regulates insulin gene expression in pancreatic beta-cells, with the transcriptional activity of ATF-2 being increased by an elevated concentration of calcium ions. |
| 847 | 10965886 | Stimulation of insulin-like growth factor binding protein-1 synthesis by interleukin-1beta: requirement of the mitogen-activated protein kinase pathway. |
| 848 | 10965886 | Insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) is a 28-kDa plasma protein that binds to IGF-I and IGF-II with high affinity. |
| 849 | 10965886 | The purpose of the present study was to investigate the role of the MAP kinase pathway in regulating IGFBP-1 synthesis by IL-1beta. |
| 850 | 10965886 | We show that IL-1beta stimulates the phosphorylation of ERK-1 and -2 in a time- and dose-dependent manner. |
| 851 | 10965886 | In addition, the MAP kinase-kinase MEK-1 and the ribosomal S6-kinase RSK-1 are also phosphorylated in response to IL-1beta. |
| 852 | 10965886 | The transcription factor CREB, a potential substrate of both protein kinase A (PKA) and RSK-1, is phosphorylated in response to IL-1beta and cAMP in HepG2 cells. |
| 853 | 10965886 | The ability of IL-1beta to stimulate the expression of IGFBP-1 and the phosphorylation of the above kinases was specifically inhibited by PD98059, a MEK-1 inhibitor. cAMP also stimulated IGFBP-1 synthesis, but PD98059 failed to block the cAMP effect. |
| 854 | 10965886 | Conversely, a PKA inhibitor (H-89) inhibited the ability of cAMP, but not IL-1beta to stimulate IGFBP-1 synthesis. |
| 855 | 10965886 | The effect of IL-1beta and cAMP on IGFBP-1 messenger RNA (mRNA) accumulation was additive. |
| 856 | 10965886 | IL-1beta, cAMP, PD98059, and H-89 had similar effects on the accumulation of IGFBP-1 protein and mRNA. |
| 857 | 10965886 | IL-1beta and cAMP did not change the half-life of IGFBP-1 mRNA, but PD98059 and SB202190, a p38 MAP kinase inhibitor, destabilized IGFBP-1 mRNA and blocked the phosphorylation of RSK-1 in response to IL-1beta. |
| 858 | 10965886 | Our data demonstrate that the MAP kinase signal transduction pathway plays an important role in the regulation of IGFBP-1 synthesis by IL-1beta. |
| 859 | 10965886 | Stimulation of insulin-like growth factor binding protein-1 synthesis by interleukin-1beta: requirement of the mitogen-activated protein kinase pathway. |
| 860 | 10965886 | Insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) is a 28-kDa plasma protein that binds to IGF-I and IGF-II with high affinity. |
| 861 | 10965886 | The purpose of the present study was to investigate the role of the MAP kinase pathway in regulating IGFBP-1 synthesis by IL-1beta. |
| 862 | 10965886 | We show that IL-1beta stimulates the phosphorylation of ERK-1 and -2 in a time- and dose-dependent manner. |
| 863 | 10965886 | In addition, the MAP kinase-kinase MEK-1 and the ribosomal S6-kinase RSK-1 are also phosphorylated in response to IL-1beta. |
| 864 | 10965886 | The transcription factor CREB, a potential substrate of both protein kinase A (PKA) and RSK-1, is phosphorylated in response to IL-1beta and cAMP in HepG2 cells. |
| 865 | 10965886 | The ability of IL-1beta to stimulate the expression of IGFBP-1 and the phosphorylation of the above kinases was specifically inhibited by PD98059, a MEK-1 inhibitor. cAMP also stimulated IGFBP-1 synthesis, but PD98059 failed to block the cAMP effect. |
| 866 | 10965886 | Conversely, a PKA inhibitor (H-89) inhibited the ability of cAMP, but not IL-1beta to stimulate IGFBP-1 synthesis. |
| 867 | 10965886 | The effect of IL-1beta and cAMP on IGFBP-1 messenger RNA (mRNA) accumulation was additive. |
| 868 | 10965886 | IL-1beta, cAMP, PD98059, and H-89 had similar effects on the accumulation of IGFBP-1 protein and mRNA. |
| 869 | 10965886 | IL-1beta and cAMP did not change the half-life of IGFBP-1 mRNA, but PD98059 and SB202190, a p38 MAP kinase inhibitor, destabilized IGFBP-1 mRNA and blocked the phosphorylation of RSK-1 in response to IL-1beta. |
| 870 | 10965886 | Our data demonstrate that the MAP kinase signal transduction pathway plays an important role in the regulation of IGFBP-1 synthesis by IL-1beta. |
| 871 | 10965886 | Stimulation of insulin-like growth factor binding protein-1 synthesis by interleukin-1beta: requirement of the mitogen-activated protein kinase pathway. |
| 872 | 10965886 | Insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) is a 28-kDa plasma protein that binds to IGF-I and IGF-II with high affinity. |
| 873 | 10965886 | The purpose of the present study was to investigate the role of the MAP kinase pathway in regulating IGFBP-1 synthesis by IL-1beta. |
| 874 | 10965886 | We show that IL-1beta stimulates the phosphorylation of ERK-1 and -2 in a time- and dose-dependent manner. |
| 875 | 10965886 | In addition, the MAP kinase-kinase MEK-1 and the ribosomal S6-kinase RSK-1 are also phosphorylated in response to IL-1beta. |
| 876 | 10965886 | The transcription factor CREB, a potential substrate of both protein kinase A (PKA) and RSK-1, is phosphorylated in response to IL-1beta and cAMP in HepG2 cells. |
| 877 | 10965886 | The ability of IL-1beta to stimulate the expression of IGFBP-1 and the phosphorylation of the above kinases was specifically inhibited by PD98059, a MEK-1 inhibitor. cAMP also stimulated IGFBP-1 synthesis, but PD98059 failed to block the cAMP effect. |
| 878 | 10965886 | Conversely, a PKA inhibitor (H-89) inhibited the ability of cAMP, but not IL-1beta to stimulate IGFBP-1 synthesis. |
| 879 | 10965886 | The effect of IL-1beta and cAMP on IGFBP-1 messenger RNA (mRNA) accumulation was additive. |
| 880 | 10965886 | IL-1beta, cAMP, PD98059, and H-89 had similar effects on the accumulation of IGFBP-1 protein and mRNA. |
| 881 | 10965886 | IL-1beta and cAMP did not change the half-life of IGFBP-1 mRNA, but PD98059 and SB202190, a p38 MAP kinase inhibitor, destabilized IGFBP-1 mRNA and blocked the phosphorylation of RSK-1 in response to IL-1beta. |
| 882 | 10965886 | Our data demonstrate that the MAP kinase signal transduction pathway plays an important role in the regulation of IGFBP-1 synthesis by IL-1beta. |
| 883 | 10977134 | Vascular endothelial growth factor (VEGF) enhances the expression of receptors and activates mitogen-activated protein (MAP) kinase of dog retinal capillary endothelial cells. |
| 884 | 10977134 | Since the galactose-fed dog is an animal model that develops the advanced stage of proliferative retinopathy, the effects of vascular endothelial growth factor (VEGF) on cell growth, receptor expression and the activation of mitogen-activated protein (MAP) kinase pathway of dog retinal capillary endothelial cells were investigated. |
| 885 | 10977134 | VEGF receptor expression was examined by RT-PCR, and activation of MAP kinase was examined with antibody against phospho-Elk-1 (Ser383). |
| 886 | 10977134 | VEGF also enhanced tube formation in dog endothelial cells and increased the expression of two VEGF receptors, Flt-1 and KDR/Flk-1. |
| 887 | 10977134 | VEGF also increases the expression of the receptors, KDR and Flt-1, and activates the p44/42 MAP kinase pathway. |
| 888 | 10977134 | Vascular endothelial growth factor (VEGF) enhances the expression of receptors and activates mitogen-activated protein (MAP) kinase of dog retinal capillary endothelial cells. |
| 889 | 10977134 | Since the galactose-fed dog is an animal model that develops the advanced stage of proliferative retinopathy, the effects of vascular endothelial growth factor (VEGF) on cell growth, receptor expression and the activation of mitogen-activated protein (MAP) kinase pathway of dog retinal capillary endothelial cells were investigated. |
| 890 | 10977134 | VEGF receptor expression was examined by RT-PCR, and activation of MAP kinase was examined with antibody against phospho-Elk-1 (Ser383). |
| 891 | 10977134 | VEGF also enhanced tube formation in dog endothelial cells and increased the expression of two VEGF receptors, Flt-1 and KDR/Flk-1. |
| 892 | 10977134 | VEGF also increases the expression of the receptors, KDR and Flt-1, and activates the p44/42 MAP kinase pathway. |
| 893 | 10977134 | Vascular endothelial growth factor (VEGF) enhances the expression of receptors and activates mitogen-activated protein (MAP) kinase of dog retinal capillary endothelial cells. |
| 894 | 10977134 | Since the galactose-fed dog is an animal model that develops the advanced stage of proliferative retinopathy, the effects of vascular endothelial growth factor (VEGF) on cell growth, receptor expression and the activation of mitogen-activated protein (MAP) kinase pathway of dog retinal capillary endothelial cells were investigated. |
| 895 | 10977134 | VEGF receptor expression was examined by RT-PCR, and activation of MAP kinase was examined with antibody against phospho-Elk-1 (Ser383). |
| 896 | 10977134 | VEGF also enhanced tube formation in dog endothelial cells and increased the expression of two VEGF receptors, Flt-1 and KDR/Flk-1. |
| 897 | 10977134 | VEGF also increases the expression of the receptors, KDR and Flt-1, and activates the p44/42 MAP kinase pathway. |
| 898 | 10977134 | Vascular endothelial growth factor (VEGF) enhances the expression of receptors and activates mitogen-activated protein (MAP) kinase of dog retinal capillary endothelial cells. |
| 899 | 10977134 | Since the galactose-fed dog is an animal model that develops the advanced stage of proliferative retinopathy, the effects of vascular endothelial growth factor (VEGF) on cell growth, receptor expression and the activation of mitogen-activated protein (MAP) kinase pathway of dog retinal capillary endothelial cells were investigated. |
| 900 | 10977134 | VEGF receptor expression was examined by RT-PCR, and activation of MAP kinase was examined with antibody against phospho-Elk-1 (Ser383). |
| 901 | 10977134 | VEGF also enhanced tube formation in dog endothelial cells and increased the expression of two VEGF receptors, Flt-1 and KDR/Flk-1. |
| 902 | 10977134 | VEGF also increases the expression of the receptors, KDR and Flt-1, and activates the p44/42 MAP kinase pathway. |
| 903 | 11006100 | In the present study we have examined the proteins involved in the insulin signaling cascade during and after differentiation of human adipocyte precursor cells and their correlation with glucose uptake. |
| 904 | 11006100 | The differentiation of human adipocytes was characterized by a two- to threefold stimulation of glucose transport in response to insulin and a marked increase protein expression for the insulin receptor, IRS-1, GLUT-4, PI 3-kinase, and PKB, with respect to undifferentiated cells. |
| 905 | 11006100 | In contrast, there were small changes in the protein expression of IRS-2, and no changes in PKC zeta and MAP kinases, although basal MAP kinase activity and GLUT-1 protein were reduced during differentiation. |
| 906 | 11006100 | In conclusion, there are quantitative differences in the regulation of IRS-1 and other proteins during differentiation which may contribute to more efficient insulin signaling leading to glucose uptake in mature fat cells. |
| 907 | 11018758 | Decreased Akt kinase activity and insulin resistance in C57BL/KsJ-Leprdb/db mice. |
| 908 | 11018758 | Recent studies suggest that the serine/threonine kinase protein kinase B (PKB or Akt) is involved in the pathway for insulin-stimulated glucose transporter 4 (GLUT4) translocation and glucose uptake. |
| 909 | 11018758 | In this study we examined the components of the Akt signaling pathway in skeletal muscle and adipose tissue in vivo from C57BL/KsJ-Lepr(db/db) mice (db/db), a model of obesity, insulin resistance, and type II diabetes. |
| 910 | 11018758 | There were no changes in the protein levels of GLUT4, p85alpha, or Akt in tissues from db/db mice compared with non-diabetic littermate controls (+/+). |
| 911 | 11018758 | In response to acute insulin administration, GLUT4 recruitment to the plasma membrane increased twofold in muscle and adipose tissue from +/+ mice, but was significantly reduced by 42-43% (P<0.05) in both tissues from db/db mice. |
| 912 | 11018758 | Insulin increased Akt-Ser(473) phosphorylation by two- to fivefold in muscle and adipose tissue from all mice. |
| 913 | 11018758 | The level of insulin-stimulated tyrosine phosphorylation of p85alpha from phosphatidylinositol 3 (PI 3)-kinase, which is upstream of Akt, was also reduced in muscle and adipose tissue from db/db mice (P<0.05); however, there was no change in extracellular signal-regulated kinase-1 or -2 phosphorylation. |
| 914 | 11018758 | These data implicate decreased insulin-stimulated Akt kinase activity as an important component underlying impaired GLUT4 translocation and insulin resistance in tissues from db/db mice. |
| 915 | 11018758 | However, impaired insulin signal transduction appears to be specific for the PI 3-kinase pathway of insulin signaling, while the MAP kinase pathway remained intact. |
| 916 | 11043572 | Tumor necrosis factor alpha-mediated insulin resistance, but not dedifferentiation, is abrogated by MEK1/2 inhibitors in 3T3-L1 adipocytes. |
| 917 | 11043572 | Tumor necrosis factor-alpha (TNFalpha) has been implicated as a contributing mediator of insulin resistance observed in pathophysiological conditions such as obesity, cancer-induced cachexia, and bacterial infections. |
| 918 | 11043572 | Previous studies have demonstrated that TNFalpha confers insulin resistance by promoting phosphorylation of serine residues on insulin receptor substrate 1 (IRS-1), thereby diminishing subsequent insulin-induced tyrosine phosphorylation of IRS-1. |
| 919 | 11043572 | However, little is known about which signaling molecules are involved in this process in adipocytes and about the temporal sequence of events that ultimately leads to TNFalpha-stimulated IRS-1 serine phosphorylation. |
| 920 | 11043572 | In this study, we demonstrate that specific inhibitors of the MAP kinase kinase (MEK)1/2-p42/44 mitogen-activated protein (MAP) kinase pathway restore insulin signaling to normal levels despite the presence of TNFalpha. |
| 921 | 11043572 | Additional experiments show that MEK1/2 activity is required for TNFalpha-induced IRS-1 serine phosphorylation, thereby suggesting a mechanism by which these inhibitors restore insulin signaling. |
| 922 | 11043572 | We observe that TNFalpha requires 2.5-4 h to markedly reduce insulin-triggered tyrosine phosphorylation of IRS-1 in 3T3-L1 adipocytes. |
| 923 | 11043572 | Although TNFalpha activates p42/44 MAP kinase, maximal stimulation is observed within 10-30 min. |
| 924 | 11043572 | To our surprise, p42/44 activity returns to basal levels well before IRS-1 serine phosphorylation and insulin resistance are observed. |
| 925 | 11043572 | These activation kinetics suggest a mechanism of p42/44 action more complicated than a direct phosphorylation of IRS-1 triggered by the early spike of TNFalpha-induced p42/44 activity. |
| 926 | 11043572 | Chronic TNFalpha treatment (>> 72 h) causes adipocyte dedifferentiation, as evidenced by the loss of triglycerides and down-regulation of adipocyte-specific markers. |
| 927 | 11043572 | We observe that this longer term TNFalpha-mediated dedifferentiation effect utilizes alternative, p42/44 MAP kinase-independent intracellular pathways. |
| 928 | 11043572 | This study suggests that TNFalpha-mediated insulin resistance, but not adipocyte dedifferentiation, is mediated by the MEK1/2-p42/44 MAP kinase pathway. |
| 929 | 11043572 | Tumor necrosis factor alpha-mediated insulin resistance, but not dedifferentiation, is abrogated by MEK1/2 inhibitors in 3T3-L1 adipocytes. |
| 930 | 11043572 | Tumor necrosis factor-alpha (TNFalpha) has been implicated as a contributing mediator of insulin resistance observed in pathophysiological conditions such as obesity, cancer-induced cachexia, and bacterial infections. |
| 931 | 11043572 | Previous studies have demonstrated that TNFalpha confers insulin resistance by promoting phosphorylation of serine residues on insulin receptor substrate 1 (IRS-1), thereby diminishing subsequent insulin-induced tyrosine phosphorylation of IRS-1. |
| 932 | 11043572 | However, little is known about which signaling molecules are involved in this process in adipocytes and about the temporal sequence of events that ultimately leads to TNFalpha-stimulated IRS-1 serine phosphorylation. |
| 933 | 11043572 | In this study, we demonstrate that specific inhibitors of the MAP kinase kinase (MEK)1/2-p42/44 mitogen-activated protein (MAP) kinase pathway restore insulin signaling to normal levels despite the presence of TNFalpha. |
| 934 | 11043572 | Additional experiments show that MEK1/2 activity is required for TNFalpha-induced IRS-1 serine phosphorylation, thereby suggesting a mechanism by which these inhibitors restore insulin signaling. |
| 935 | 11043572 | We observe that TNFalpha requires 2.5-4 h to markedly reduce insulin-triggered tyrosine phosphorylation of IRS-1 in 3T3-L1 adipocytes. |
| 936 | 11043572 | Although TNFalpha activates p42/44 MAP kinase, maximal stimulation is observed within 10-30 min. |
| 937 | 11043572 | To our surprise, p42/44 activity returns to basal levels well before IRS-1 serine phosphorylation and insulin resistance are observed. |
| 938 | 11043572 | These activation kinetics suggest a mechanism of p42/44 action more complicated than a direct phosphorylation of IRS-1 triggered by the early spike of TNFalpha-induced p42/44 activity. |
| 939 | 11043572 | Chronic TNFalpha treatment (>> 72 h) causes adipocyte dedifferentiation, as evidenced by the loss of triglycerides and down-regulation of adipocyte-specific markers. |
| 940 | 11043572 | We observe that this longer term TNFalpha-mediated dedifferentiation effect utilizes alternative, p42/44 MAP kinase-independent intracellular pathways. |
| 941 | 11043572 | This study suggests that TNFalpha-mediated insulin resistance, but not adipocyte dedifferentiation, is mediated by the MEK1/2-p42/44 MAP kinase pathway. |
| 942 | 11043572 | Tumor necrosis factor alpha-mediated insulin resistance, but not dedifferentiation, is abrogated by MEK1/2 inhibitors in 3T3-L1 adipocytes. |
| 943 | 11043572 | Tumor necrosis factor-alpha (TNFalpha) has been implicated as a contributing mediator of insulin resistance observed in pathophysiological conditions such as obesity, cancer-induced cachexia, and bacterial infections. |
| 944 | 11043572 | Previous studies have demonstrated that TNFalpha confers insulin resistance by promoting phosphorylation of serine residues on insulin receptor substrate 1 (IRS-1), thereby diminishing subsequent insulin-induced tyrosine phosphorylation of IRS-1. |
| 945 | 11043572 | However, little is known about which signaling molecules are involved in this process in adipocytes and about the temporal sequence of events that ultimately leads to TNFalpha-stimulated IRS-1 serine phosphorylation. |
| 946 | 11043572 | In this study, we demonstrate that specific inhibitors of the MAP kinase kinase (MEK)1/2-p42/44 mitogen-activated protein (MAP) kinase pathway restore insulin signaling to normal levels despite the presence of TNFalpha. |
| 947 | 11043572 | Additional experiments show that MEK1/2 activity is required for TNFalpha-induced IRS-1 serine phosphorylation, thereby suggesting a mechanism by which these inhibitors restore insulin signaling. |
| 948 | 11043572 | We observe that TNFalpha requires 2.5-4 h to markedly reduce insulin-triggered tyrosine phosphorylation of IRS-1 in 3T3-L1 adipocytes. |
| 949 | 11043572 | Although TNFalpha activates p42/44 MAP kinase, maximal stimulation is observed within 10-30 min. |
| 950 | 11043572 | To our surprise, p42/44 activity returns to basal levels well before IRS-1 serine phosphorylation and insulin resistance are observed. |
| 951 | 11043572 | These activation kinetics suggest a mechanism of p42/44 action more complicated than a direct phosphorylation of IRS-1 triggered by the early spike of TNFalpha-induced p42/44 activity. |
| 952 | 11043572 | Chronic TNFalpha treatment (>> 72 h) causes adipocyte dedifferentiation, as evidenced by the loss of triglycerides and down-regulation of adipocyte-specific markers. |
| 953 | 11043572 | We observe that this longer term TNFalpha-mediated dedifferentiation effect utilizes alternative, p42/44 MAP kinase-independent intracellular pathways. |
| 954 | 11043572 | This study suggests that TNFalpha-mediated insulin resistance, but not adipocyte dedifferentiation, is mediated by the MEK1/2-p42/44 MAP kinase pathway. |
| 955 | 11043572 | Tumor necrosis factor alpha-mediated insulin resistance, but not dedifferentiation, is abrogated by MEK1/2 inhibitors in 3T3-L1 adipocytes. |
| 956 | 11043572 | Tumor necrosis factor-alpha (TNFalpha) has been implicated as a contributing mediator of insulin resistance observed in pathophysiological conditions such as obesity, cancer-induced cachexia, and bacterial infections. |
| 957 | 11043572 | Previous studies have demonstrated that TNFalpha confers insulin resistance by promoting phosphorylation of serine residues on insulin receptor substrate 1 (IRS-1), thereby diminishing subsequent insulin-induced tyrosine phosphorylation of IRS-1. |
| 958 | 11043572 | However, little is known about which signaling molecules are involved in this process in adipocytes and about the temporal sequence of events that ultimately leads to TNFalpha-stimulated IRS-1 serine phosphorylation. |
| 959 | 11043572 | In this study, we demonstrate that specific inhibitors of the MAP kinase kinase (MEK)1/2-p42/44 mitogen-activated protein (MAP) kinase pathway restore insulin signaling to normal levels despite the presence of TNFalpha. |
| 960 | 11043572 | Additional experiments show that MEK1/2 activity is required for TNFalpha-induced IRS-1 serine phosphorylation, thereby suggesting a mechanism by which these inhibitors restore insulin signaling. |
| 961 | 11043572 | We observe that TNFalpha requires 2.5-4 h to markedly reduce insulin-triggered tyrosine phosphorylation of IRS-1 in 3T3-L1 adipocytes. |
| 962 | 11043572 | Although TNFalpha activates p42/44 MAP kinase, maximal stimulation is observed within 10-30 min. |
| 963 | 11043572 | To our surprise, p42/44 activity returns to basal levels well before IRS-1 serine phosphorylation and insulin resistance are observed. |
| 964 | 11043572 | These activation kinetics suggest a mechanism of p42/44 action more complicated than a direct phosphorylation of IRS-1 triggered by the early spike of TNFalpha-induced p42/44 activity. |
| 965 | 11043572 | Chronic TNFalpha treatment (>> 72 h) causes adipocyte dedifferentiation, as evidenced by the loss of triglycerides and down-regulation of adipocyte-specific markers. |
| 966 | 11043572 | We observe that this longer term TNFalpha-mediated dedifferentiation effect utilizes alternative, p42/44 MAP kinase-independent intracellular pathways. |
| 967 | 11043572 | This study suggests that TNFalpha-mediated insulin resistance, but not adipocyte dedifferentiation, is mediated by the MEK1/2-p42/44 MAP kinase pathway. |
| 968 | 11125222 | Insulin-induced swelling is essential for generating the antiproteolytic response to the hormone, which depends on activation of the MAP-kinase p38. |
| 969 | 11125222 | Cell swelling by insulin is Ptdins-3-kinase mediated and contributes to the activation of Erk- and p38-type MAP-kinases. |
| 970 | 11125222 | In liver, hyperosmolarity impairs the Ptdins-3-kinase-dependent K(+) uptake and cell swelling in response to insulin, leading to resistance of MAP-kinases and proteolysis to regulation by insulin. |
| 971 | 11125222 | Likewise, a reduction of insulin-induced swelling by the loop diuretics furosemide and bumetanide cause insulin resistance shown by the levels of cell swelling, MAP-kinase activation and proteolysis control. |
| 972 | 11125222 | Insulin-induced swelling is essential for generating the antiproteolytic response to the hormone, which depends on activation of the MAP-kinase p38. |
| 973 | 11125222 | Cell swelling by insulin is Ptdins-3-kinase mediated and contributes to the activation of Erk- and p38-type MAP-kinases. |
| 974 | 11125222 | In liver, hyperosmolarity impairs the Ptdins-3-kinase-dependent K(+) uptake and cell swelling in response to insulin, leading to resistance of MAP-kinases and proteolysis to regulation by insulin. |
| 975 | 11125222 | Likewise, a reduction of insulin-induced swelling by the loop diuretics furosemide and bumetanide cause insulin resistance shown by the levels of cell swelling, MAP-kinase activation and proteolysis control. |
| 976 | 11237210 | Ras activation of the Raf kinase: tyrosine kinase recruitment of the MAP kinase cascade. |
| 977 | 11237210 | Nevertheless, based on the hypothesis that insulin-stimulated Ser/Thr phosphorylation reflected the activation of protein (Ser/Thr) kinases downstream of the insulin receptor, we sought to detect and purify these putative, insulin-responsive protein (Ser/Thr) kinases. |
| 978 | 11237210 | The first of these insulin-activated protein kinase networks to be fully elucidated was the Ras-Raf-mitogen-activated protein kinase (MAPK) cascade. |
| 979 | 11237210 | This chapter will summarize briefly the way in which work from this and other laboratories on insulin signaling led to the discovery of the mammalian MAP kinase cascade and, in turn, to the identification of unique role of the Raf kinases in RTK activation of this protein (Ser/Thr) kinase cascade. |
| 980 | 11237210 | Ras activation of the Raf kinase: tyrosine kinase recruitment of the MAP kinase cascade. |
| 981 | 11237210 | Nevertheless, based on the hypothesis that insulin-stimulated Ser/Thr phosphorylation reflected the activation of protein (Ser/Thr) kinases downstream of the insulin receptor, we sought to detect and purify these putative, insulin-responsive protein (Ser/Thr) kinases. |
| 982 | 11237210 | The first of these insulin-activated protein kinase networks to be fully elucidated was the Ras-Raf-mitogen-activated protein kinase (MAPK) cascade. |
| 983 | 11237210 | This chapter will summarize briefly the way in which work from this and other laboratories on insulin signaling led to the discovery of the mammalian MAP kinase cascade and, in turn, to the identification of unique role of the Raf kinases in RTK activation of this protein (Ser/Thr) kinase cascade. |
| 984 | 11375351 | Inhibitors of protein kinase C (PKC) and p38 mitogen-activated protein (MAP) kinase also reduced the hypoxia-induced stimulation of proliferation and OPN synthesis. |
| 985 | 11375351 | In conclusion, hypoxia-induced proliferation of cultured VSM cells is mediated by the stimulation of OPN synthesis involving PKC and p38 MAP kinase. |
| 986 | 11423472 | Transcriptional regulation of plasminogen activator inhibitor type 1 gene by insulin: insights into the signaling pathway. |
| 987 | 11423472 | Impairment of the fibrinolytic system, caused primarily by increases in the plasma levels of plasminogen activator inhibitor (PAI) type 1, are frequently found in diabetes and the insulin-resistance syndrome. |
| 988 | 11423472 | Among the factors responsible for the increases of PAI-1, insulin has recently attracted attention. |
| 989 | 11423472 | In this study, we analyzed the effects of insulin on PAI-1 biosynthesis in HepG2 cells, paying particular attention to the signaling network evoked by this hormone. |
| 990 | 11423472 | Experiments performed in CHO cells overexpressing the insulin receptor indicate that insulin increases PAI-1 gene transcription through interaction with its receptor. |
| 991 | 11423472 | By using inhibitors of the different signaling pathways evoked by insulin-receptor binding, it has been shown that the biosynthesis of PAI-1 is due to phosphatidylinositol (PI) 3-kinase activation, followed by protein kinase C and ultimately by mitogen-activated protein (MAP) kinase activation and extracellular signal-regulated kinase 2 phosphorylation. |
| 992 | 11423472 | Transfection of HepG2 cells with several truncations of the PAI-1 promoter coupled to a CAT gene allowed us to recognize two major response elements located in the regions between -804 and -708 and between -211 and -54. |
| 993 | 11423472 | Electrophoretic mobility shift assay identified three binding sites for insulin-induced factors, all colocalized with putative Sp1 binding sites. |
| 994 | 11423472 | Using supershifting antibodies, the binding of Sp1 could only be confirmed at the binding site located just upstream from the transcription start site of the PAI-1 promoter. |
| 995 | 11423472 | A construct comprising four tandem repeat copies of the -93/-62 region of the PAI-1 promoter linked to CAT was transcriptionally activated in HepG2 cells by insulin. |
| 996 | 11423472 | These results outline the central role of MAP kinase activation in the regulation of PAI-1 induced by insulin. |
| 997 | 11423472 | Transcriptional regulation of plasminogen activator inhibitor type 1 gene by insulin: insights into the signaling pathway. |
| 998 | 11423472 | Impairment of the fibrinolytic system, caused primarily by increases in the plasma levels of plasminogen activator inhibitor (PAI) type 1, are frequently found in diabetes and the insulin-resistance syndrome. |
| 999 | 11423472 | Among the factors responsible for the increases of PAI-1, insulin has recently attracted attention. |
| 1000 | 11423472 | In this study, we analyzed the effects of insulin on PAI-1 biosynthesis in HepG2 cells, paying particular attention to the signaling network evoked by this hormone. |
| 1001 | 11423472 | Experiments performed in CHO cells overexpressing the insulin receptor indicate that insulin increases PAI-1 gene transcription through interaction with its receptor. |
| 1002 | 11423472 | By using inhibitors of the different signaling pathways evoked by insulin-receptor binding, it has been shown that the biosynthesis of PAI-1 is due to phosphatidylinositol (PI) 3-kinase activation, followed by protein kinase C and ultimately by mitogen-activated protein (MAP) kinase activation and extracellular signal-regulated kinase 2 phosphorylation. |
| 1003 | 11423472 | Transfection of HepG2 cells with several truncations of the PAI-1 promoter coupled to a CAT gene allowed us to recognize two major response elements located in the regions between -804 and -708 and between -211 and -54. |
| 1004 | 11423472 | Electrophoretic mobility shift assay identified three binding sites for insulin-induced factors, all colocalized with putative Sp1 binding sites. |
| 1005 | 11423472 | Using supershifting antibodies, the binding of Sp1 could only be confirmed at the binding site located just upstream from the transcription start site of the PAI-1 promoter. |
| 1006 | 11423472 | A construct comprising four tandem repeat copies of the -93/-62 region of the PAI-1 promoter linked to CAT was transcriptionally activated in HepG2 cells by insulin. |
| 1007 | 11423472 | These results outline the central role of MAP kinase activation in the regulation of PAI-1 induced by insulin. |
| 1008 | 11423478 | We demonstrated that when embryonic day 13.5 rat pancreatic epithelium is cultured in the presence of PD98059, an inhibitor of the mitogen-activated protein (MAP) kinase, epithelial cell proliferation is decreased, whereas endocrine cell differentiation is activated. |
| 1009 | 11423478 | On the other hand, in the presence of epidermal growth factor (EGF), an activator of the MAP kinase pathway, the mass of tissue that develops is increased, whereas the absolute number of endocrine cells that develops is decreased. |
| 1010 | 11423478 | In a second step, when EGF is removed from the pool of immature pancreatic epithelial cells, the cells differentiate en masse into insulin-expressing cells. |
| 1011 | 11423478 | We demonstrated that when embryonic day 13.5 rat pancreatic epithelium is cultured in the presence of PD98059, an inhibitor of the mitogen-activated protein (MAP) kinase, epithelial cell proliferation is decreased, whereas endocrine cell differentiation is activated. |
| 1012 | 11423478 | On the other hand, in the presence of epidermal growth factor (EGF), an activator of the MAP kinase pathway, the mass of tissue that develops is increased, whereas the absolute number of endocrine cells that develops is decreased. |
| 1013 | 11423478 | In a second step, when EGF is removed from the pool of immature pancreatic epithelial cells, the cells differentiate en masse into insulin-expressing cells. |
| 1014 | 11440359 | Activation of DAG-sensitive PKC isoforms, such as PKC-theta and PKC-epsilon, down-regulates insulin receptor signalling and could be an important biochemical mechanism linking dysregulated lipid metabolism and insulin resistance in muscle. |
| 1015 | 11440359 | On the other hand, atypical PKC isozymes, such as PKC-zeta and PKC-lambda, have been identified as downstream targets of PI-3-kinase involved in insulin-stimulated glucose uptake, especially in adipocytes. |
| 1016 | 11440359 | Glucose-induced de novo synthesis of (palmitate-rich) DAG and sustained isozyme-selective PKC activation (especially but not exclusively PKC-beta) has been strongly implicated in the pathogenesis of diabetic microangiopathy and macroangiopathy through a host of undesirable effects on endothelial function, VSM contractility and growth, angiogenesis, gene transcription (in part by MAP-kinase activation) and vascular permeability. |
| 1017 | 11466584 | Beside their regulation by different metabolites, these transcription factors are also targets of hormones, like insulin and leptin, growth factors, and inflammatory signals. |
| 1018 | 11466584 | Major signalling pathways coupling receptors at the cell surface for hormones, growth factors as well as cytokines to gene regulatory events in the nucleus are the MAP-kinase cascades. |
| 1019 | 11472733 | Glucosamine enhances platelet-derived growth factor-induced DNA synthesis via phosphatidylinositol 3-kinase pathway in rat aortic smooth muscle cells. |
| 1020 | 11472733 | Culture of vascular smooth muscle A10 cells with high glucose for 4 weeks enhanced platelet-derived growth factor (PDGF)-induced BrdU incorporation. |
| 1021 | 11472733 | Of the subsequent intracellular signaling pathways, PDGF-induced PDGF beta-receptor association with PLC gamma was not affected, whereas tyrosine phosphorylation of Shc, subsequent association of Shc with Grb2, and MAP kinase activation were relatively decreased. |
| 1022 | 11472733 | In contrast, PDGF-induced PDGF beta-receptor association with the p85 regulatory subunit of PI3-kinase and PI3-kinase activation were increased by 20% (P<0.01) and 36% (P<0.01), respectively. |
| 1023 | 11472733 | Pretreatment with PLC inhibitor (U73122) had negligible effects, and MEK1 inhibitor (PD98059) showed only a slight inhibitory effect on the PDGF-induced BrdU incorporation. |
| 1024 | 11472733 | In contrast, pretreatment with PI3-kinase inhibitor (LY294002) significantly inhibited glucosamine enhancement of PDGF-induced BrdU incorporation. |
| 1025 | 11472733 | These findings suggest that glucosamine is involved in the development of atherosclerosis by enhancing PDGF-induced mitogenesis specifically via the PI3-kinase pathway. |
| 1026 | 11561209 | Herein, a focal point is the mitochondrial control of specific death enzymes--so called caspases--by members of the pro-apoptotic Bax and BH3 subfamily or the anti-apoptotic Bcl-2 subfamily. |
| 1027 | 11561209 | The insulin-like growth factors (IGFs) are potent proliferation factors and potently inhibit apoptosis acting via the ubiquitously expressed IGF-I receptor. |
| 1028 | 11561209 | Within IGF-I receptor signalling, key to the inhibition of apoptosis are the RAS/RAF/mitogen-activated protein (MAP)-kinase pathway and the PI 3'-kinase pathway. |
| 1029 | 11574421 | To determine whether enzymatic p53 glycosylation leads to angiotensin II formation followed by p53 phosphorylation, prolonged activation of the renin-angiotensin system, and apoptosis, ventricular myocytes were exposed to levels of glucose mimicking diabetic hyperglycemia. |
| 1030 | 11574421 | Angiotensin II synthesis increased at 45 min and 1 h, resulting in p38 mitogen-activated protein (MAP) kinase-driven p53 phosphorylation at Ser 390. p53 phosphorylation was absent at the early time points, becoming evident at 1 h, and increasing progressively from 3 h to 4 days. |
| 1031 | 11574421 | Phosphorylated p53 at Ser 18 and activated c-Jun NH(2)-terminal kinases were identified with hyperglycemia, whereas extracellular signal-regulated kinase was not phosphorylated. |
| 1032 | 11574421 | Upregulation of p53 was associated with an accumulation of angiotensinogen and AT(1) and enhanced production of angiotensin II. |
| 1033 | 11574421 | Inhibition of O-glycosylation prevented the initial synthesis of angiotensin II, p53, and p38-MAP kinase (MAPK) phosphorylation and apoptosis. |
| 1034 | 11574421 | AT(1) blockade had no influence on O-glycosylation of p53, but it interfered with p53 phosphorylation; losartan also prevented phosphorylation of p38-MAPK by angiotensin II. |
| 1035 | 11574421 | In conclusion, these in vitro results support the notion that hyperglycemia with diabetes promotes myocyte apoptosis mediated by activation of p53 and effector responses involving the local renin-angiotensin system. |
| 1036 | 11576932 | In mesangial and endothelial cells, the AGE-RAGE interaction caused enhanced formation of oxygen radicals with subsequent activation of nuclear factor-kappaB and release of pro-inflammatory cytokines (interleukin-6, tumor necrosis factor-alpha), growth factors (transforming growth factor-beta1 [TGF-beta1], insulin-like growth factor-1), and adhesion molecules (vascular cell adhesion molecule-1, intercellular adhesion molecule-1). |
| 1037 | 11576932 | In tubular cells, incubation with AGE albumin was followed by stimulation of the mitogen-activating protein (MAP) kinase pathway and its downstream target, the activating protien-1 (AP-1) complex, TGF-beta1 overexpression, enhanced protein kinase C activity, decreased cell proliferation, and impaired protein degradation rate, in part caused by decreased cathepsin activities. |
| 1038 | 11576932 | The pathogenic relevance of AGEs was further verified by in vivo experiments in euglycemic rats and mice by the parenteral administration of AGE albumin, leading in the glomeruli to TGF-beta1 overproduction, enhanced gene expression of ECM proteins, and morphological lesions similar to those of DN. |
| 1039 | 11689013 | Tumor necrosis factor alpha is a negative regulator of resistin gene expression and secretion in 3T3-L1 adipocytes. |
| 1040 | 11689013 | Resistin has recently been implicated as an adipocytokine leading to insulin resistance and, therefore, potentially linking obesity and diabetes. |
| 1041 | 11689013 | To further characterize the regulation of this fat-secreted protein by insulin sensitivity-modulating hormones, 3T3-L1 adipocytes were treated with tumor necrosis factor (TNF) alpha, angiotensin (AT) 2, as well as growth hormone (GH), and resistin gene expression and protein secretion were determined by quantitative real-time reverse transcription-polymerase chain reaction and Western blotting. |
| 1042 | 11689013 | Interestingly, both, resistin mRNA expression and protein secretion, were inhibited by 70-90% after TNFalpha-treatment whereas AT2 and GH did not have any effect. |
| 1043 | 11689013 | Pharmacological inhibition of protein kinase A (PKA), p44/42, and p38 mitogen-activated protein (MAP) kinase did not reverse the inhibitory effect of TNFalpha suggesting that neither of these signaling molecules is involved in suppression of resistin gene expression by TNFalpha. |
| 1044 | 11689013 | Furthermore, suppression of resistin mRNA levels could be completely reversed to control levels by withdrawal of TNFalpha for 24 h. |
| 1045 | 11689013 | Taken together, these results suggest that TNFalpha is a pivotal negative regulator of resistin gene expression. |
| 1046 | 11700025 | RAGE expression and AGE-induced MAP kinase activation in Caco-2 cells. |
| 1047 | 11700025 | Since RAGE ligation triggers the p21(ras) signal transduction pathway the activation state of p44/42 (ERK1/2) MAP kinases was determined. |
| 1048 | 11700025 | Here we demonstrate for the first time that Caco-2 cells express RAGE and that administration of the food-derived casein-linked AGE N(epsilon)-(carboxymethyl)lysine (Cas-CML) results in Caco-2 p44/42 (ERK1/2) MAP kinase activation. |
| 1049 | 11700025 | RAGE expression and AGE-induced MAP kinase activation in Caco-2 cells. |
| 1050 | 11700025 | Since RAGE ligation triggers the p21(ras) signal transduction pathway the activation state of p44/42 (ERK1/2) MAP kinases was determined. |
| 1051 | 11700025 | Here we demonstrate for the first time that Caco-2 cells express RAGE and that administration of the food-derived casein-linked AGE N(epsilon)-(carboxymethyl)lysine (Cas-CML) results in Caco-2 p44/42 (ERK1/2) MAP kinase activation. |
| 1052 | 11707433 | Inhibition of phosphatidylinositol 3-kinase enhances mitogenic actions of insulin in endothelial cells. |
| 1053 | 11707433 | To explore this hypothesis in endothelial cells, we designed a set of experiments to mimic the "typical metabolic insulin resistance" by blocking the phosphatidylinositol 3-kinase pathway and exposing the cells to increasing concentrations of insulin ("compensatory hyperinsulinemia"). |
| 1054 | 11707433 | Inhibition of phosphatidylinositol 3-kinase with wortmannin blocked the ability of insulin to stimulate increased expression of endothelial nitric-oxide synthase, did not affect insulin-induced activation of MAP kinase, and increased the effects of insulin on prenylation of Ras and Rho proteins. |
| 1055 | 11711055 | Hypertension often complicates type 2 diabetes mellitus, and angiotensin converting enzyme inhibitor treatment has been shown to improve insulin resistance in such cases. |
| 1056 | 11711055 | However, the effect of angiotensin II type-1 (AT(1)) receptor antagonists on insulin resistance is still controversial. |
| 1057 | 11711055 | Although Akt activity and glucose transporter type 4 (GLUT4) expressions were not affected by losartan with or without exercise, extracellular signal-regulated kinase (ERK1/2) and p38 mitogen-activated protein (MAP) kinase activities were increased by both interventions. |
| 1058 | 11711055 | These results indicate that angiotensin AT(1) receptor antagonist improved local insulin resistance, but not systemic insulin resistance. |
| 1059 | 11711055 | These findings may explain the controversy over the effect of angiotensin AT(1) receptor antagonists on insulin resistance in clinical use. |
| 1060 | 11711055 | The enhancing effect of angiotensin AT(1) receptor antagonist on skeletal muscle glucose uptake may be attributable to MAP kinase activation or other mechanisms rather than phosphatidylinositol 3-kinase activation. |
| 1061 | 11711055 | Hypertension often complicates type 2 diabetes mellitus, and angiotensin converting enzyme inhibitor treatment has been shown to improve insulin resistance in such cases. |
| 1062 | 11711055 | However, the effect of angiotensin II type-1 (AT(1)) receptor antagonists on insulin resistance is still controversial. |
| 1063 | 11711055 | Although Akt activity and glucose transporter type 4 (GLUT4) expressions were not affected by losartan with or without exercise, extracellular signal-regulated kinase (ERK1/2) and p38 mitogen-activated protein (MAP) kinase activities were increased by both interventions. |
| 1064 | 11711055 | These results indicate that angiotensin AT(1) receptor antagonist improved local insulin resistance, but not systemic insulin resistance. |
| 1065 | 11711055 | These findings may explain the controversy over the effect of angiotensin AT(1) receptor antagonists on insulin resistance in clinical use. |
| 1066 | 11711055 | The enhancing effect of angiotensin AT(1) receptor antagonist on skeletal muscle glucose uptake may be attributable to MAP kinase activation or other mechanisms rather than phosphatidylinositol 3-kinase activation. |
| 1067 | 11719827 | These haemodynamic pathways, independently and with metabolic pathways, activate intracellular second messengers such as protein kinase C and MAP kinase, nuclear transcription factors such as NF-kappaB and various growth factors such as the prosclerotic cytokine, TGF-beta and the angiogenic, permeability enhancing growth factor, VEGF. |
| 1068 | 11719827 | More novel strategies to influence vasoactive hormone action or to inhibit various metabolic pathways such as inhibitors of advanced glycation, specific protein kinase C isoforms and aldose reductase are at present under experimental and clinical investigation. |
| 1069 | 11826398 | Insulin signaling in the transcriptional and posttranscriptional regulation of CYP2E1 expression. |
| 1070 | 11826398 | Diabetes has been reported to increase the expression of cytochrome P450 (CYP) 2E1 messenger RNA (mRNA) and protein several-fold, and enhanced expression has been associated with elevated ketone bodies. |
| 1071 | 11826398 | Primary cultured rat hepatocytes were used to explore ketone body and insulin regulation of CYP2E1 expression. |
| 1072 | 11826398 | Insulin produced a concentration-dependent decrease in CYP2E1 mRNA levels, and insulin receptor immunoprecipitation showed a correspondence between receptor phosphorylation and the decrease in CYP2E1 mRNA levels at physiologic levels of insulin. |
| 1073 | 11826398 | The phosphatidylinositol 3-kinase (PI3-kinase) inhibitors wortmannin or LY294002 and rapamycin, an inhibitor of p70 S6 kinase phosphorylation, ameliorated the insulin-mediated decrease in CYP2E1 mRNA levels. |
| 1074 | 11826398 | Geldanamycin, which inhibits Src kinase, also abrogated the insulin-mediated decrease in CYP2E1 mRNA levels. |
| 1075 | 11826398 | In contrast, the protein kinase C (PKC) inhibitor bisindolylmaleimide, the mitogen-activated protein kinase kinase (MEK) inhibitor PD98059, and the p38 mitogen-activated protein (MAP) kinase inhibitor SB202190 did not affect the insulin-mediated decrease in CYP2E1. |
| 1076 | 11826398 | CYP2E1 mRNA half-life decreased from approximately 48 hours in the absence of insulin to approximately 15 hours at 10 nmol/L insulin, and this decrease was prevented by wortmannin. |
| 1077 | 11826398 | The half-life of CYP2B mRNA was increased by insulin, whereas that of CYP3A was unaffected. |
| 1078 | 11826398 | Analysis of CYP2E1 gene transcription using heterogeneous nuclear RNA (hnRNA) showed that insulin suppressed CYP2E1 transcription. |
| 1079 | 11826398 | In conclusion, these data show involvement of transcriptional and posttranscriptional mechanisms in the insulin-mediated regulation of CYP2E1 and implicate PI3-kinase, p70 S6 kinase, and Src kinase in mediating these effects. |
| 1080 | 11911852 | Exendin-4 increases insulin sensitivity via a PI-3-kinase-dependent mechanism: contrasting effects of GLP-1. |
| 1081 | 11911852 | The insulinotropic agent, exendin-4, is a long-acting analogue of glucagon-like peptide-1 (GLP-1) which improves glucose tolerance in humans and animals with diabetes, but the underlying mechanisms and the effects of exendin-4 on peripheral (muscle/fat) insulin action are unclear. |
| 1082 | 11911852 | Thus, the comparative effects of exendin-4 and GLP-1 on insulin-stimulated 2-[3H]deoxyglucose (2-DOG) uptake were measured in fully differentiated L6 myotubes and 3T3-adipocytes, including co-incubation with inhibitors of the PI-3-kinase (wortmannin) and mitogen-activated protein (MAP) kinase (PD098059) pathways. |
| 1083 | 11911852 | In L6 myotubes, there was a concentration-dependent and PI-3-kinase-dependent increase in insulin-stimulated 2-DOG uptake with exendin-4 and GLP-1, e.g. for exendin-4 the C(I-200) value (concentration of insulin required to increase 2-DOG uptake 2-fold) decreased from 1.3 +/- 1.4 x 10(-7)M (insulin alone, n=16) to 5.9 +/- 1.3 x 10(-8)M (insulin+exendin-4 0.1nM, n=18, P<0.03). |
| 1084 | 11911852 | A similar insulin-sensitizing effect was observed with exendin-4 in 3T3-adipocytes, but GLP-1 had no effect on adipocyte insulin sensitivity. |
| 1085 | 11911852 | Furthermore, the contrasting responses of exendin and GLP-1 in 3T3-adipocytes suggest that the peripheral insulin-sensitizing effect of exendin-4 (in contrast to the insulinotropic effect) does not involve the GLP-1 receptor pathway. |
| 1086 | 11991199 | Potentiation of mitogenic activity of platelet-derived growth factor by physiological concentrations of insulin via the MAP kinase cascade in rat A10 vascular smooth muscle cells. |
| 1087 | 11991199 | In this study, we attempted to determine whether insulin affects mitogenic signaling induced by platelet-derived growth factor (PDGF) in a rat VSMC cell line (A10 cells). |
| 1088 | 11991199 | Initiation of DNA synthesis was preceded by activation of Raf-1, MEK and MAP kinases (Erk 1 and Erk2). |
| 1089 | 11991199 | Treatment of the cells with PD98059, an inhibitor of MAPK kinase (MEK) attenuated but did not abolish PDGF-stimulated DNA synthesis, suggesting that MAPK is required but not essential for DNA synthesis. |
| 1090 | 11991199 | PDGF also stimulated phosphorylation of protein kinase B (Akt/PKB) and p70 S6Kinase (p70S6K) in a wortmannin-sensitive manner. |
| 1091 | 11991199 | Low concentrations of insulin (1-10 nmol/l) alone showed little mitogenic activity and no significant effect on MAPK activity. |
| 1092 | 11991199 | However, the presence of insulin enhanced both DNA synthesis and MAPK activation by PDGF. |
| 1093 | 11991199 | Insulin was without effect on PDGF-stimulated activations of protein kinase B (Akt/PKB) and p70S6K. |
| 1094 | 11991199 | We conclude that insulin, at pathophysiologically relevant concentrations, potentiates the PDGF-stimulated DNA synthesis, at least in part, by potentiating activation of the MAPK cascade. |
| 1095 | 12000720 | Angiopoietin-1, when given intravitreally to newly diabetic rats, normalized retinal vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 mRNA and protein levels, leading to reductions in leukocyte adhesion, endothelial cell injury, and blood-retinal barrier breakdown. |
| 1096 | 12000720 | These changes coincided with reductions in retinal eNOS, nitric oxide, Akt (protein kinase B), and MAP kinase activity, known mediators of VEGF bioactivity and leukocyte adhesion. |
| 1097 | 12000720 | When endogenous VEGF bioactivity was inhibited with a soluble Flt-1/Fc chimera, retinal Akt kinase activity was significantly reduced in vivo. |
| 1098 | 12012272 | Effect of epidermal growth factor (EGF) on steroid and cyclic nucleotide secretion, proliferation and ERK-related MAP-kinase in cultured rabbit granulosa cells. |
| 1099 | 12012272 | The influence of EGF on steroidogenesis, proliferation, cyclic nucleotides and MAP-kinase in rabbit granulosa cells were studied. |
| 1100 | 12012272 | Immunocytochemical study demonstrated an EGF-induced (10 ng/ml) increase in the proportion of cells revealing proliferating cell nuclear antigen (41% vs 24.7% in control, p < 0.01). |
| 1101 | 12012272 | EGF (10 ng/ml) increased the proportion of cells with immunoreactivity to ERK-1 (more than two-fold) and ERK-3 (three-fold) members of the MAP-kinase family. |
| 1102 | 12012272 | Moreover, EGF induced the translocation of ERK-1 to the nucleus, whilst preferentially cytoplasmic localization of ERK-3 was not changed after EGF addition. |
| 1103 | 12012272 | This can indicate regulation of ERK-1 and -3 by EGF, as well as differential patterns of ERK-1 and ERK-3 expression in response to EGF in cultured granulosa cells. - These results indicate that EGF can be a stimulator of proliferation, steroidogenesis and cyclic nucleotide release by rabbit granulosa cells. |
| 1104 | 12012272 | Stimulation of cAMP and cGMP release, and activation of ERK-related MAP kinase in granulosa cells after EGF addition indicates the involvement of these intracellular messengers in mediating the EGF action on the ovary. |
| 1105 | 12012272 | Effect of epidermal growth factor (EGF) on steroid and cyclic nucleotide secretion, proliferation and ERK-related MAP-kinase in cultured rabbit granulosa cells. |
| 1106 | 12012272 | The influence of EGF on steroidogenesis, proliferation, cyclic nucleotides and MAP-kinase in rabbit granulosa cells were studied. |
| 1107 | 12012272 | Immunocytochemical study demonstrated an EGF-induced (10 ng/ml) increase in the proportion of cells revealing proliferating cell nuclear antigen (41% vs 24.7% in control, p < 0.01). |
| 1108 | 12012272 | EGF (10 ng/ml) increased the proportion of cells with immunoreactivity to ERK-1 (more than two-fold) and ERK-3 (three-fold) members of the MAP-kinase family. |
| 1109 | 12012272 | Moreover, EGF induced the translocation of ERK-1 to the nucleus, whilst preferentially cytoplasmic localization of ERK-3 was not changed after EGF addition. |
| 1110 | 12012272 | This can indicate regulation of ERK-1 and -3 by EGF, as well as differential patterns of ERK-1 and ERK-3 expression in response to EGF in cultured granulosa cells. - These results indicate that EGF can be a stimulator of proliferation, steroidogenesis and cyclic nucleotide release by rabbit granulosa cells. |
| 1111 | 12012272 | Stimulation of cAMP and cGMP release, and activation of ERK-related MAP kinase in granulosa cells after EGF addition indicates the involvement of these intracellular messengers in mediating the EGF action on the ovary. |
| 1112 | 12012272 | Effect of epidermal growth factor (EGF) on steroid and cyclic nucleotide secretion, proliferation and ERK-related MAP-kinase in cultured rabbit granulosa cells. |
| 1113 | 12012272 | The influence of EGF on steroidogenesis, proliferation, cyclic nucleotides and MAP-kinase in rabbit granulosa cells were studied. |
| 1114 | 12012272 | Immunocytochemical study demonstrated an EGF-induced (10 ng/ml) increase in the proportion of cells revealing proliferating cell nuclear antigen (41% vs 24.7% in control, p < 0.01). |
| 1115 | 12012272 | EGF (10 ng/ml) increased the proportion of cells with immunoreactivity to ERK-1 (more than two-fold) and ERK-3 (three-fold) members of the MAP-kinase family. |
| 1116 | 12012272 | Moreover, EGF induced the translocation of ERK-1 to the nucleus, whilst preferentially cytoplasmic localization of ERK-3 was not changed after EGF addition. |
| 1117 | 12012272 | This can indicate regulation of ERK-1 and -3 by EGF, as well as differential patterns of ERK-1 and ERK-3 expression in response to EGF in cultured granulosa cells. - These results indicate that EGF can be a stimulator of proliferation, steroidogenesis and cyclic nucleotide release by rabbit granulosa cells. |
| 1118 | 12012272 | Stimulation of cAMP and cGMP release, and activation of ERK-related MAP kinase in granulosa cells after EGF addition indicates the involvement of these intracellular messengers in mediating the EGF action on the ovary. |
| 1119 | 12012272 | Effect of epidermal growth factor (EGF) on steroid and cyclic nucleotide secretion, proliferation and ERK-related MAP-kinase in cultured rabbit granulosa cells. |
| 1120 | 12012272 | The influence of EGF on steroidogenesis, proliferation, cyclic nucleotides and MAP-kinase in rabbit granulosa cells were studied. |
| 1121 | 12012272 | Immunocytochemical study demonstrated an EGF-induced (10 ng/ml) increase in the proportion of cells revealing proliferating cell nuclear antigen (41% vs 24.7% in control, p < 0.01). |
| 1122 | 12012272 | EGF (10 ng/ml) increased the proportion of cells with immunoreactivity to ERK-1 (more than two-fold) and ERK-3 (three-fold) members of the MAP-kinase family. |
| 1123 | 12012272 | Moreover, EGF induced the translocation of ERK-1 to the nucleus, whilst preferentially cytoplasmic localization of ERK-3 was not changed after EGF addition. |
| 1124 | 12012272 | This can indicate regulation of ERK-1 and -3 by EGF, as well as differential patterns of ERK-1 and ERK-3 expression in response to EGF in cultured granulosa cells. - These results indicate that EGF can be a stimulator of proliferation, steroidogenesis and cyclic nucleotide release by rabbit granulosa cells. |
| 1125 | 12012272 | Stimulation of cAMP and cGMP release, and activation of ERK-related MAP kinase in granulosa cells after EGF addition indicates the involvement of these intracellular messengers in mediating the EGF action on the ovary. |
| 1126 | 12079831 | Besides their regulation by metabolites and nutrients, these transcription factors are also targets of hormones (like insulin and leptin), growth factors, inflammatory signals, and drugs. |
| 1127 | 12079831 | Major signaling pathways coupling transcription factors to extracellular stimuli are the MAP kinase cascades. |
| 1128 | 12079831 | We have recently shown that SREBPs appear to be substrates of MAP kinases and propose that SREBP-1 might play a role in the development of cellular features belonging to lipid toxicity and possibly syndrome X. |
| 1129 | 12124776 | Exendin-4 differentiation of a human pancreatic duct cell line into endocrine cells: involvement of PDX-1 and HNF3beta transcription factors. |
| 1130 | 12124776 | Western blot analysis detected a progressive increase in protein levels of glucokinase and GLUT2 over 3 days of EX-4 treatment. |
| 1131 | 12124776 | We explored the sequence of activation of certain transcription factors known to be essential for the beta cell phenotype: PDX-1, Beta2/NeuroD, and hepatocyte nuclear factor 3beta (HNF3beta). |
| 1132 | 12124776 | Double immunostaining showed that PDX-1 coexisted with insulin and glucagon in EX-4-treated cells. |
| 1133 | 12124776 | EMSA results indicated that EX-4 caused a 12-fold increase in HNF3beta binding to PDX-1 promoter area II. |
| 1134 | 12124776 | Differentiation to insulin-producing cells was also seen when Capan-1 cells were transfected with pdx-1, with 80% of these cells expressing insulin 3 days after transfection. |
| 1135 | 12124776 | During the differentiation of duct cells to endocrine cells, cAMP levels (EX-4 is a ligand for the GLP-1, G-protein coupled receptor) and MAP kinase activity increased. |
| 1136 | 12124776 | Our results indicate that EX-4 activates adenylyl cyclase and MAP kinase which, in turn, may lead to activation of transcription factors necessary for an endocrine phenotype. |
| 1137 | 12124776 | Exendin-4 differentiation of a human pancreatic duct cell line into endocrine cells: involvement of PDX-1 and HNF3beta transcription factors. |
| 1138 | 12124776 | Western blot analysis detected a progressive increase in protein levels of glucokinase and GLUT2 over 3 days of EX-4 treatment. |
| 1139 | 12124776 | We explored the sequence of activation of certain transcription factors known to be essential for the beta cell phenotype: PDX-1, Beta2/NeuroD, and hepatocyte nuclear factor 3beta (HNF3beta). |
| 1140 | 12124776 | Double immunostaining showed that PDX-1 coexisted with insulin and glucagon in EX-4-treated cells. |
| 1141 | 12124776 | EMSA results indicated that EX-4 caused a 12-fold increase in HNF3beta binding to PDX-1 promoter area II. |
| 1142 | 12124776 | Differentiation to insulin-producing cells was also seen when Capan-1 cells were transfected with pdx-1, with 80% of these cells expressing insulin 3 days after transfection. |
| 1143 | 12124776 | During the differentiation of duct cells to endocrine cells, cAMP levels (EX-4 is a ligand for the GLP-1, G-protein coupled receptor) and MAP kinase activity increased. |
| 1144 | 12124776 | Our results indicate that EX-4 activates adenylyl cyclase and MAP kinase which, in turn, may lead to activation of transcription factors necessary for an endocrine phenotype. |
| 1145 | 12135597 | The pentapeptide displaces cell membrane-bound C-peptide, elicits transient increase in intracellular Ca(2+) concentration and stimulates MAP kinase signalling pathways and Na(+),K(+)-ATPase. |
| 1146 | 12369712 | Role of protein kinase C, PI3-kinase and tyrosine kinase in activation of MAP kinase by glucose and agonists of G-protein coupled receptors in INS-1 cells. |
| 1147 | 12369712 | The interplay of protein kinase C (PKC), PI3-kinase and cellular tyrosine kinase with MAP kinase activity using inhibitors and compounds such as glucose, phorbol 12-myristate 13-acetate (PMA) and agonists of G-protein coupled receptors like gastrin releasing peptide (GRP), oxytocin (OT) and glucose-dependent insulinotropic peptide (GIP) was investigated in INS-1 cells, an insulin secreting cell line. |
| 1148 | 12369712 | MAP kinase activity was determined by using a peptide derived from the EGF receptor as a MAP kinase substrate and [32P]ATP. |
| 1149 | 12369712 | Glucose as well as GRP, OT and GIP exhibited a time-dependent increase in MAP kinase activity with a maximum at time point 2.5 min. |
| 1150 | 12369712 | The flavone PD 098059 is known to bind to the inactive forms of MEK1 (MAPK/ERK-Kinase) thus preventing activation by upstream activators. 20 microM PD 098059 (IC50 = 5 microM) inhibited MAP kinase stimulated by either glucose, GRP, OT, GIP or PMA. |
| 1151 | 12369712 | Inhibiton ("downregulation") of PKC by a long term (22 h) pretreatment with 1 microM PMA did not influence MAP kinase activity when augmented by either of the above mentioned compound. |
| 1152 | 12369712 | To investigate whether PI3-kinase and cellular tyrosine kinase are involved in G-protein mediated effects on MAP kinase, inhibitors were used: 100 nM wortmannin (PI3-kinase inhibitor) reduced the effects of GRP, OT and GIP but not that of PMA; 100 microM genistein (tyrosine kinase inhibitor) inhibited the stimulatory effect of either above mentioned compound on MAP kinase activation. |
| 1153 | 12369712 | Inhibition of MAP kinase by 20 microM PD 098059 did not influence insulin secretion modulated by either compound (glucose, GRP, OT or GIP). [3H]Thymidine incorporation, however, was severely inhibited by PD 098059. |
| 1154 | 12369712 | Thus MAP kinase is important for INS-1 cell proliferation but not for its insulin secretory response with respect to major initiators and modulators of insulin release. |
| 1155 | 12369712 | The data indicate that MAP kinase is active and under the control of MAP kinase. |
| 1156 | 12369712 | PKC is upstream of a genistein-sensitive tyrosine kinase and probably downstream of a PI3-kinase in INS-1 cells. |
| 1157 | 12369712 | Role of protein kinase C, PI3-kinase and tyrosine kinase in activation of MAP kinase by glucose and agonists of G-protein coupled receptors in INS-1 cells. |
| 1158 | 12369712 | The interplay of protein kinase C (PKC), PI3-kinase and cellular tyrosine kinase with MAP kinase activity using inhibitors and compounds such as glucose, phorbol 12-myristate 13-acetate (PMA) and agonists of G-protein coupled receptors like gastrin releasing peptide (GRP), oxytocin (OT) and glucose-dependent insulinotropic peptide (GIP) was investigated in INS-1 cells, an insulin secreting cell line. |
| 1159 | 12369712 | MAP kinase activity was determined by using a peptide derived from the EGF receptor as a MAP kinase substrate and [32P]ATP. |
| 1160 | 12369712 | Glucose as well as GRP, OT and GIP exhibited a time-dependent increase in MAP kinase activity with a maximum at time point 2.5 min. |
| 1161 | 12369712 | The flavone PD 098059 is known to bind to the inactive forms of MEK1 (MAPK/ERK-Kinase) thus preventing activation by upstream activators. 20 microM PD 098059 (IC50 = 5 microM) inhibited MAP kinase stimulated by either glucose, GRP, OT, GIP or PMA. |
| 1162 | 12369712 | Inhibiton ("downregulation") of PKC by a long term (22 h) pretreatment with 1 microM PMA did not influence MAP kinase activity when augmented by either of the above mentioned compound. |
| 1163 | 12369712 | To investigate whether PI3-kinase and cellular tyrosine kinase are involved in G-protein mediated effects on MAP kinase, inhibitors were used: 100 nM wortmannin (PI3-kinase inhibitor) reduced the effects of GRP, OT and GIP but not that of PMA; 100 microM genistein (tyrosine kinase inhibitor) inhibited the stimulatory effect of either above mentioned compound on MAP kinase activation. |
| 1164 | 12369712 | Inhibition of MAP kinase by 20 microM PD 098059 did not influence insulin secretion modulated by either compound (glucose, GRP, OT or GIP). [3H]Thymidine incorporation, however, was severely inhibited by PD 098059. |
| 1165 | 12369712 | Thus MAP kinase is important for INS-1 cell proliferation but not for its insulin secretory response with respect to major initiators and modulators of insulin release. |
| 1166 | 12369712 | The data indicate that MAP kinase is active and under the control of MAP kinase. |
| 1167 | 12369712 | PKC is upstream of a genistein-sensitive tyrosine kinase and probably downstream of a PI3-kinase in INS-1 cells. |
| 1168 | 12369712 | Role of protein kinase C, PI3-kinase and tyrosine kinase in activation of MAP kinase by glucose and agonists of G-protein coupled receptors in INS-1 cells. |
| 1169 | 12369712 | The interplay of protein kinase C (PKC), PI3-kinase and cellular tyrosine kinase with MAP kinase activity using inhibitors and compounds such as glucose, phorbol 12-myristate 13-acetate (PMA) and agonists of G-protein coupled receptors like gastrin releasing peptide (GRP), oxytocin (OT) and glucose-dependent insulinotropic peptide (GIP) was investigated in INS-1 cells, an insulin secreting cell line. |
| 1170 | 12369712 | MAP kinase activity was determined by using a peptide derived from the EGF receptor as a MAP kinase substrate and [32P]ATP. |
| 1171 | 12369712 | Glucose as well as GRP, OT and GIP exhibited a time-dependent increase in MAP kinase activity with a maximum at time point 2.5 min. |
| 1172 | 12369712 | The flavone PD 098059 is known to bind to the inactive forms of MEK1 (MAPK/ERK-Kinase) thus preventing activation by upstream activators. 20 microM PD 098059 (IC50 = 5 microM) inhibited MAP kinase stimulated by either glucose, GRP, OT, GIP or PMA. |
| 1173 | 12369712 | Inhibiton ("downregulation") of PKC by a long term (22 h) pretreatment with 1 microM PMA did not influence MAP kinase activity when augmented by either of the above mentioned compound. |
| 1174 | 12369712 | To investigate whether PI3-kinase and cellular tyrosine kinase are involved in G-protein mediated effects on MAP kinase, inhibitors were used: 100 nM wortmannin (PI3-kinase inhibitor) reduced the effects of GRP, OT and GIP but not that of PMA; 100 microM genistein (tyrosine kinase inhibitor) inhibited the stimulatory effect of either above mentioned compound on MAP kinase activation. |
| 1175 | 12369712 | Inhibition of MAP kinase by 20 microM PD 098059 did not influence insulin secretion modulated by either compound (glucose, GRP, OT or GIP). [3H]Thymidine incorporation, however, was severely inhibited by PD 098059. |
| 1176 | 12369712 | Thus MAP kinase is important for INS-1 cell proliferation but not for its insulin secretory response with respect to major initiators and modulators of insulin release. |
| 1177 | 12369712 | The data indicate that MAP kinase is active and under the control of MAP kinase. |
| 1178 | 12369712 | PKC is upstream of a genistein-sensitive tyrosine kinase and probably downstream of a PI3-kinase in INS-1 cells. |
| 1179 | 12369712 | Role of protein kinase C, PI3-kinase and tyrosine kinase in activation of MAP kinase by glucose and agonists of G-protein coupled receptors in INS-1 cells. |
| 1180 | 12369712 | The interplay of protein kinase C (PKC), PI3-kinase and cellular tyrosine kinase with MAP kinase activity using inhibitors and compounds such as glucose, phorbol 12-myristate 13-acetate (PMA) and agonists of G-protein coupled receptors like gastrin releasing peptide (GRP), oxytocin (OT) and glucose-dependent insulinotropic peptide (GIP) was investigated in INS-1 cells, an insulin secreting cell line. |
| 1181 | 12369712 | MAP kinase activity was determined by using a peptide derived from the EGF receptor as a MAP kinase substrate and [32P]ATP. |
| 1182 | 12369712 | Glucose as well as GRP, OT and GIP exhibited a time-dependent increase in MAP kinase activity with a maximum at time point 2.5 min. |
| 1183 | 12369712 | The flavone PD 098059 is known to bind to the inactive forms of MEK1 (MAPK/ERK-Kinase) thus preventing activation by upstream activators. 20 microM PD 098059 (IC50 = 5 microM) inhibited MAP kinase stimulated by either glucose, GRP, OT, GIP or PMA. |
| 1184 | 12369712 | Inhibiton ("downregulation") of PKC by a long term (22 h) pretreatment with 1 microM PMA did not influence MAP kinase activity when augmented by either of the above mentioned compound. |
| 1185 | 12369712 | To investigate whether PI3-kinase and cellular tyrosine kinase are involved in G-protein mediated effects on MAP kinase, inhibitors were used: 100 nM wortmannin (PI3-kinase inhibitor) reduced the effects of GRP, OT and GIP but not that of PMA; 100 microM genistein (tyrosine kinase inhibitor) inhibited the stimulatory effect of either above mentioned compound on MAP kinase activation. |
| 1186 | 12369712 | Inhibition of MAP kinase by 20 microM PD 098059 did not influence insulin secretion modulated by either compound (glucose, GRP, OT or GIP). [3H]Thymidine incorporation, however, was severely inhibited by PD 098059. |
| 1187 | 12369712 | Thus MAP kinase is important for INS-1 cell proliferation but not for its insulin secretory response with respect to major initiators and modulators of insulin release. |
| 1188 | 12369712 | The data indicate that MAP kinase is active and under the control of MAP kinase. |
| 1189 | 12369712 | PKC is upstream of a genistein-sensitive tyrosine kinase and probably downstream of a PI3-kinase in INS-1 cells. |
| 1190 | 12369712 | Role of protein kinase C, PI3-kinase and tyrosine kinase in activation of MAP kinase by glucose and agonists of G-protein coupled receptors in INS-1 cells. |
| 1191 | 12369712 | The interplay of protein kinase C (PKC), PI3-kinase and cellular tyrosine kinase with MAP kinase activity using inhibitors and compounds such as glucose, phorbol 12-myristate 13-acetate (PMA) and agonists of G-protein coupled receptors like gastrin releasing peptide (GRP), oxytocin (OT) and glucose-dependent insulinotropic peptide (GIP) was investigated in INS-1 cells, an insulin secreting cell line. |
| 1192 | 12369712 | MAP kinase activity was determined by using a peptide derived from the EGF receptor as a MAP kinase substrate and [32P]ATP. |
| 1193 | 12369712 | Glucose as well as GRP, OT and GIP exhibited a time-dependent increase in MAP kinase activity with a maximum at time point 2.5 min. |
| 1194 | 12369712 | The flavone PD 098059 is known to bind to the inactive forms of MEK1 (MAPK/ERK-Kinase) thus preventing activation by upstream activators. 20 microM PD 098059 (IC50 = 5 microM) inhibited MAP kinase stimulated by either glucose, GRP, OT, GIP or PMA. |
| 1195 | 12369712 | Inhibiton ("downregulation") of PKC by a long term (22 h) pretreatment with 1 microM PMA did not influence MAP kinase activity when augmented by either of the above mentioned compound. |
| 1196 | 12369712 | To investigate whether PI3-kinase and cellular tyrosine kinase are involved in G-protein mediated effects on MAP kinase, inhibitors were used: 100 nM wortmannin (PI3-kinase inhibitor) reduced the effects of GRP, OT and GIP but not that of PMA; 100 microM genistein (tyrosine kinase inhibitor) inhibited the stimulatory effect of either above mentioned compound on MAP kinase activation. |
| 1197 | 12369712 | Inhibition of MAP kinase by 20 microM PD 098059 did not influence insulin secretion modulated by either compound (glucose, GRP, OT or GIP). [3H]Thymidine incorporation, however, was severely inhibited by PD 098059. |
| 1198 | 12369712 | Thus MAP kinase is important for INS-1 cell proliferation but not for its insulin secretory response with respect to major initiators and modulators of insulin release. |
| 1199 | 12369712 | The data indicate that MAP kinase is active and under the control of MAP kinase. |
| 1200 | 12369712 | PKC is upstream of a genistein-sensitive tyrosine kinase and probably downstream of a PI3-kinase in INS-1 cells. |
| 1201 | 12369712 | Role of protein kinase C, PI3-kinase and tyrosine kinase in activation of MAP kinase by glucose and agonists of G-protein coupled receptors in INS-1 cells. |
| 1202 | 12369712 | The interplay of protein kinase C (PKC), PI3-kinase and cellular tyrosine kinase with MAP kinase activity using inhibitors and compounds such as glucose, phorbol 12-myristate 13-acetate (PMA) and agonists of G-protein coupled receptors like gastrin releasing peptide (GRP), oxytocin (OT) and glucose-dependent insulinotropic peptide (GIP) was investigated in INS-1 cells, an insulin secreting cell line. |
| 1203 | 12369712 | MAP kinase activity was determined by using a peptide derived from the EGF receptor as a MAP kinase substrate and [32P]ATP. |
| 1204 | 12369712 | Glucose as well as GRP, OT and GIP exhibited a time-dependent increase in MAP kinase activity with a maximum at time point 2.5 min. |
| 1205 | 12369712 | The flavone PD 098059 is known to bind to the inactive forms of MEK1 (MAPK/ERK-Kinase) thus preventing activation by upstream activators. 20 microM PD 098059 (IC50 = 5 microM) inhibited MAP kinase stimulated by either glucose, GRP, OT, GIP or PMA. |
| 1206 | 12369712 | Inhibiton ("downregulation") of PKC by a long term (22 h) pretreatment with 1 microM PMA did not influence MAP kinase activity when augmented by either of the above mentioned compound. |
| 1207 | 12369712 | To investigate whether PI3-kinase and cellular tyrosine kinase are involved in G-protein mediated effects on MAP kinase, inhibitors were used: 100 nM wortmannin (PI3-kinase inhibitor) reduced the effects of GRP, OT and GIP but not that of PMA; 100 microM genistein (tyrosine kinase inhibitor) inhibited the stimulatory effect of either above mentioned compound on MAP kinase activation. |
| 1208 | 12369712 | Inhibition of MAP kinase by 20 microM PD 098059 did not influence insulin secretion modulated by either compound (glucose, GRP, OT or GIP). [3H]Thymidine incorporation, however, was severely inhibited by PD 098059. |
| 1209 | 12369712 | Thus MAP kinase is important for INS-1 cell proliferation but not for its insulin secretory response with respect to major initiators and modulators of insulin release. |
| 1210 | 12369712 | The data indicate that MAP kinase is active and under the control of MAP kinase. |
| 1211 | 12369712 | PKC is upstream of a genistein-sensitive tyrosine kinase and probably downstream of a PI3-kinase in INS-1 cells. |
| 1212 | 12369712 | Role of protein kinase C, PI3-kinase and tyrosine kinase in activation of MAP kinase by glucose and agonists of G-protein coupled receptors in INS-1 cells. |
| 1213 | 12369712 | The interplay of protein kinase C (PKC), PI3-kinase and cellular tyrosine kinase with MAP kinase activity using inhibitors and compounds such as glucose, phorbol 12-myristate 13-acetate (PMA) and agonists of G-protein coupled receptors like gastrin releasing peptide (GRP), oxytocin (OT) and glucose-dependent insulinotropic peptide (GIP) was investigated in INS-1 cells, an insulin secreting cell line. |
| 1214 | 12369712 | MAP kinase activity was determined by using a peptide derived from the EGF receptor as a MAP kinase substrate and [32P]ATP. |
| 1215 | 12369712 | Glucose as well as GRP, OT and GIP exhibited a time-dependent increase in MAP kinase activity with a maximum at time point 2.5 min. |
| 1216 | 12369712 | The flavone PD 098059 is known to bind to the inactive forms of MEK1 (MAPK/ERK-Kinase) thus preventing activation by upstream activators. 20 microM PD 098059 (IC50 = 5 microM) inhibited MAP kinase stimulated by either glucose, GRP, OT, GIP or PMA. |
| 1217 | 12369712 | Inhibiton ("downregulation") of PKC by a long term (22 h) pretreatment with 1 microM PMA did not influence MAP kinase activity when augmented by either of the above mentioned compound. |
| 1218 | 12369712 | To investigate whether PI3-kinase and cellular tyrosine kinase are involved in G-protein mediated effects on MAP kinase, inhibitors were used: 100 nM wortmannin (PI3-kinase inhibitor) reduced the effects of GRP, OT and GIP but not that of PMA; 100 microM genistein (tyrosine kinase inhibitor) inhibited the stimulatory effect of either above mentioned compound on MAP kinase activation. |
| 1219 | 12369712 | Inhibition of MAP kinase by 20 microM PD 098059 did not influence insulin secretion modulated by either compound (glucose, GRP, OT or GIP). [3H]Thymidine incorporation, however, was severely inhibited by PD 098059. |
| 1220 | 12369712 | Thus MAP kinase is important for INS-1 cell proliferation but not for its insulin secretory response with respect to major initiators and modulators of insulin release. |
| 1221 | 12369712 | The data indicate that MAP kinase is active and under the control of MAP kinase. |
| 1222 | 12369712 | PKC is upstream of a genistein-sensitive tyrosine kinase and probably downstream of a PI3-kinase in INS-1 cells. |
| 1223 | 12369712 | Role of protein kinase C, PI3-kinase and tyrosine kinase in activation of MAP kinase by glucose and agonists of G-protein coupled receptors in INS-1 cells. |
| 1224 | 12369712 | The interplay of protein kinase C (PKC), PI3-kinase and cellular tyrosine kinase with MAP kinase activity using inhibitors and compounds such as glucose, phorbol 12-myristate 13-acetate (PMA) and agonists of G-protein coupled receptors like gastrin releasing peptide (GRP), oxytocin (OT) and glucose-dependent insulinotropic peptide (GIP) was investigated in INS-1 cells, an insulin secreting cell line. |
| 1225 | 12369712 | MAP kinase activity was determined by using a peptide derived from the EGF receptor as a MAP kinase substrate and [32P]ATP. |
| 1226 | 12369712 | Glucose as well as GRP, OT and GIP exhibited a time-dependent increase in MAP kinase activity with a maximum at time point 2.5 min. |
| 1227 | 12369712 | The flavone PD 098059 is known to bind to the inactive forms of MEK1 (MAPK/ERK-Kinase) thus preventing activation by upstream activators. 20 microM PD 098059 (IC50 = 5 microM) inhibited MAP kinase stimulated by either glucose, GRP, OT, GIP or PMA. |
| 1228 | 12369712 | Inhibiton ("downregulation") of PKC by a long term (22 h) pretreatment with 1 microM PMA did not influence MAP kinase activity when augmented by either of the above mentioned compound. |
| 1229 | 12369712 | To investigate whether PI3-kinase and cellular tyrosine kinase are involved in G-protein mediated effects on MAP kinase, inhibitors were used: 100 nM wortmannin (PI3-kinase inhibitor) reduced the effects of GRP, OT and GIP but not that of PMA; 100 microM genistein (tyrosine kinase inhibitor) inhibited the stimulatory effect of either above mentioned compound on MAP kinase activation. |
| 1230 | 12369712 | Inhibition of MAP kinase by 20 microM PD 098059 did not influence insulin secretion modulated by either compound (glucose, GRP, OT or GIP). [3H]Thymidine incorporation, however, was severely inhibited by PD 098059. |
| 1231 | 12369712 | Thus MAP kinase is important for INS-1 cell proliferation but not for its insulin secretory response with respect to major initiators and modulators of insulin release. |
| 1232 | 12369712 | The data indicate that MAP kinase is active and under the control of MAP kinase. |
| 1233 | 12369712 | PKC is upstream of a genistein-sensitive tyrosine kinase and probably downstream of a PI3-kinase in INS-1 cells. |
| 1234 | 12369712 | Role of protein kinase C, PI3-kinase and tyrosine kinase in activation of MAP kinase by glucose and agonists of G-protein coupled receptors in INS-1 cells. |
| 1235 | 12369712 | The interplay of protein kinase C (PKC), PI3-kinase and cellular tyrosine kinase with MAP kinase activity using inhibitors and compounds such as glucose, phorbol 12-myristate 13-acetate (PMA) and agonists of G-protein coupled receptors like gastrin releasing peptide (GRP), oxytocin (OT) and glucose-dependent insulinotropic peptide (GIP) was investigated in INS-1 cells, an insulin secreting cell line. |
| 1236 | 12369712 | MAP kinase activity was determined by using a peptide derived from the EGF receptor as a MAP kinase substrate and [32P]ATP. |
| 1237 | 12369712 | Glucose as well as GRP, OT and GIP exhibited a time-dependent increase in MAP kinase activity with a maximum at time point 2.5 min. |
| 1238 | 12369712 | The flavone PD 098059 is known to bind to the inactive forms of MEK1 (MAPK/ERK-Kinase) thus preventing activation by upstream activators. 20 microM PD 098059 (IC50 = 5 microM) inhibited MAP kinase stimulated by either glucose, GRP, OT, GIP or PMA. |
| 1239 | 12369712 | Inhibiton ("downregulation") of PKC by a long term (22 h) pretreatment with 1 microM PMA did not influence MAP kinase activity when augmented by either of the above mentioned compound. |
| 1240 | 12369712 | To investigate whether PI3-kinase and cellular tyrosine kinase are involved in G-protein mediated effects on MAP kinase, inhibitors were used: 100 nM wortmannin (PI3-kinase inhibitor) reduced the effects of GRP, OT and GIP but not that of PMA; 100 microM genistein (tyrosine kinase inhibitor) inhibited the stimulatory effect of either above mentioned compound on MAP kinase activation. |
| 1241 | 12369712 | Inhibition of MAP kinase by 20 microM PD 098059 did not influence insulin secretion modulated by either compound (glucose, GRP, OT or GIP). [3H]Thymidine incorporation, however, was severely inhibited by PD 098059. |
| 1242 | 12369712 | Thus MAP kinase is important for INS-1 cell proliferation but not for its insulin secretory response with respect to major initiators and modulators of insulin release. |
| 1243 | 12369712 | The data indicate that MAP kinase is active and under the control of MAP kinase. |
| 1244 | 12369712 | PKC is upstream of a genistein-sensitive tyrosine kinase and probably downstream of a PI3-kinase in INS-1 cells. |
| 1245 | 12369712 | Role of protein kinase C, PI3-kinase and tyrosine kinase in activation of MAP kinase by glucose and agonists of G-protein coupled receptors in INS-1 cells. |
| 1246 | 12369712 | The interplay of protein kinase C (PKC), PI3-kinase and cellular tyrosine kinase with MAP kinase activity using inhibitors and compounds such as glucose, phorbol 12-myristate 13-acetate (PMA) and agonists of G-protein coupled receptors like gastrin releasing peptide (GRP), oxytocin (OT) and glucose-dependent insulinotropic peptide (GIP) was investigated in INS-1 cells, an insulin secreting cell line. |
| 1247 | 12369712 | MAP kinase activity was determined by using a peptide derived from the EGF receptor as a MAP kinase substrate and [32P]ATP. |
| 1248 | 12369712 | Glucose as well as GRP, OT and GIP exhibited a time-dependent increase in MAP kinase activity with a maximum at time point 2.5 min. |
| 1249 | 12369712 | The flavone PD 098059 is known to bind to the inactive forms of MEK1 (MAPK/ERK-Kinase) thus preventing activation by upstream activators. 20 microM PD 098059 (IC50 = 5 microM) inhibited MAP kinase stimulated by either glucose, GRP, OT, GIP or PMA. |
| 1250 | 12369712 | Inhibiton ("downregulation") of PKC by a long term (22 h) pretreatment with 1 microM PMA did not influence MAP kinase activity when augmented by either of the above mentioned compound. |
| 1251 | 12369712 | To investigate whether PI3-kinase and cellular tyrosine kinase are involved in G-protein mediated effects on MAP kinase, inhibitors were used: 100 nM wortmannin (PI3-kinase inhibitor) reduced the effects of GRP, OT and GIP but not that of PMA; 100 microM genistein (tyrosine kinase inhibitor) inhibited the stimulatory effect of either above mentioned compound on MAP kinase activation. |
| 1252 | 12369712 | Inhibition of MAP kinase by 20 microM PD 098059 did not influence insulin secretion modulated by either compound (glucose, GRP, OT or GIP). [3H]Thymidine incorporation, however, was severely inhibited by PD 098059. |
| 1253 | 12369712 | Thus MAP kinase is important for INS-1 cell proliferation but not for its insulin secretory response with respect to major initiators and modulators of insulin release. |
| 1254 | 12369712 | The data indicate that MAP kinase is active and under the control of MAP kinase. |
| 1255 | 12369712 | PKC is upstream of a genistein-sensitive tyrosine kinase and probably downstream of a PI3-kinase in INS-1 cells. |
| 1256 | 12485893 | Inhibition of p38 MAP kinase corrects biochemical and neurological deficits in experimental diabetic neuropathy. |
| 1257 | 12485893 | Diabetes is known to activate MAP kinase p38 in sensory neurons in both rats and patients. |
| 1258 | 12485893 | Consequently we tested the hypothesis that inhibition of MAP kinase p38 might prevent neuronal dysfunction in rats with experimental diabetes, such as the classical defect of slowed nerve conduction. |
| 1259 | 12485893 | This implicates activation of MAP kinase p38 as an early step in the signal pathway to dysfunction in experimental diabetic neuropathy. |
| 1260 | 12485893 | Inhibition of p38 MAP kinase corrects biochemical and neurological deficits in experimental diabetic neuropathy. |
| 1261 | 12485893 | Diabetes is known to activate MAP kinase p38 in sensory neurons in both rats and patients. |
| 1262 | 12485893 | Consequently we tested the hypothesis that inhibition of MAP kinase p38 might prevent neuronal dysfunction in rats with experimental diabetes, such as the classical defect of slowed nerve conduction. |
| 1263 | 12485893 | This implicates activation of MAP kinase p38 as an early step in the signal pathway to dysfunction in experimental diabetic neuropathy. |
| 1264 | 12485893 | Inhibition of p38 MAP kinase corrects biochemical and neurological deficits in experimental diabetic neuropathy. |
| 1265 | 12485893 | Diabetes is known to activate MAP kinase p38 in sensory neurons in both rats and patients. |
| 1266 | 12485893 | Consequently we tested the hypothesis that inhibition of MAP kinase p38 might prevent neuronal dysfunction in rats with experimental diabetes, such as the classical defect of slowed nerve conduction. |
| 1267 | 12485893 | This implicates activation of MAP kinase p38 as an early step in the signal pathway to dysfunction in experimental diabetic neuropathy. |
| 1268 | 12606502 | Enhanced basal activation of mitogen-activated protein kinases in adipocytes from type 2 diabetes: potential role of p38 in the downregulation of GLUT4 expression. |
| 1269 | 12606502 | To test the potential for members of the mitogen-activated protein (MAP) kinase family to contribute to type 2 diabetes, we examined basal and insulin-stimulated Erk 1/2, JNK, and p38 phosphorylation in adipocytes isolated from healthy and type 2 diabetic individuals. |
| 1270 | 12606502 | Maximal insulin stimulation increased the phosphorylation of Erk 1/2 and JNK in healthy control subjects but not type 2 diabetic patients. |
| 1271 | 12606502 | Insulin stimulation did not increase p38 phosphorylation in either healthy control subjects or type 2 diabetic patients. |
| 1272 | 12606502 | In type 2 diabetic adipocytes, the basal phosphorylation status of these MAP kinases was significantly elevated and was associated with decreased IRS-1 and GLUT4 in these fat cells. |
| 1273 | 12606502 | To determine whether MAP kinases were involved in the downregulation of IRS-1 and GLUT4 protein levels, selective inhibitors were used to inhibit these MAP kinases in 3T3-L1 adipocytes treated chronically with insulin. |
| 1274 | 12606502 | Inhibition of Erk 1/2, JNK, or p38 had no effect on insulin-stimulated reduction of IRS-1 protein levels. |
| 1275 | 12606502 | However, inhibition of the p38 pathway prevented the insulin-stimulated decrease in GLUT4 protein levels. |
| 1276 | 12606502 | In summary, type 2 diabetes is associated with an increased basal activation of the MAP kinase family. |
| 1277 | 12606502 | Furthermore, upregulation of the p38 pathway might contribute to the loss of GLUT4 expression observed in adipose tissue from type 2 diabetic patients. |
| 1278 | 12606502 | Enhanced basal activation of mitogen-activated protein kinases in adipocytes from type 2 diabetes: potential role of p38 in the downregulation of GLUT4 expression. |
| 1279 | 12606502 | To test the potential for members of the mitogen-activated protein (MAP) kinase family to contribute to type 2 diabetes, we examined basal and insulin-stimulated Erk 1/2, JNK, and p38 phosphorylation in adipocytes isolated from healthy and type 2 diabetic individuals. |
| 1280 | 12606502 | Maximal insulin stimulation increased the phosphorylation of Erk 1/2 and JNK in healthy control subjects but not type 2 diabetic patients. |
| 1281 | 12606502 | Insulin stimulation did not increase p38 phosphorylation in either healthy control subjects or type 2 diabetic patients. |
| 1282 | 12606502 | In type 2 diabetic adipocytes, the basal phosphorylation status of these MAP kinases was significantly elevated and was associated with decreased IRS-1 and GLUT4 in these fat cells. |
| 1283 | 12606502 | To determine whether MAP kinases were involved in the downregulation of IRS-1 and GLUT4 protein levels, selective inhibitors were used to inhibit these MAP kinases in 3T3-L1 adipocytes treated chronically with insulin. |
| 1284 | 12606502 | Inhibition of Erk 1/2, JNK, or p38 had no effect on insulin-stimulated reduction of IRS-1 protein levels. |
| 1285 | 12606502 | However, inhibition of the p38 pathway prevented the insulin-stimulated decrease in GLUT4 protein levels. |
| 1286 | 12606502 | In summary, type 2 diabetes is associated with an increased basal activation of the MAP kinase family. |
| 1287 | 12606502 | Furthermore, upregulation of the p38 pathway might contribute to the loss of GLUT4 expression observed in adipose tissue from type 2 diabetic patients. |
| 1288 | 12621526 | Incubation with D-glucose activated protein kinase C (PKC), endothelial NO synthase (eNOS), p42 and p44 mitogen-activated protein kinases (p42/44(mapk)), but inhibited superoxide dismutase (SOD). |
| 1289 | 12621526 | The effect of D-glucose was blocked by the PKC inhibitor calphostin C, the MAP kinase kinase 1/2 (MEK1/2) inhibitor PD-98059, the eNOS inhibitor L-NAME, the protein kinase G (PKG) inhibitor KT-5823 and the protein kinase A (PKA) inhibitor KT-5720. |
| 1290 | 12621526 | D-Glucose-dependent inhibition of thymidine incorporation and cell proliferation is associated with increased PKC, eNOS, and MEK1/2, but decreased SOD activity, and higher intracellular levels of cGMP, cAMP and Ca2+ in HUVECs. |
| 1291 | 12777378 | Dual specificity mitogen-activated protein (MAP) kinase phosphatase-4 plays a potential role in insulin resistance. |
| 1292 | 12777378 | Specifically, a reporter system comprised of the PEPCK promoter upstream of alkaline phosphatase was used in a hepatocyte cell-based assay to screen an expression cDNA library for genes that reverse insulin-induced repression of PEPCK transcription. |
| 1293 | 12777378 | Here we show that MKP-4 is expressed in insulin-responsive tissues and that the expression levels are up-regulated in obese insulin-resistant rodent models. |
| 1294 | 12777378 | Heterologous expression of MKP-4 in preadipocytes significantly blocked insulin-induced adipogenesis, and overexpression of MKP-4 in adipocytes inhibited insulin-stimulated glucose uptake. |
| 1295 | 12777378 | Our data suggest that MKP-4 negatively regulates insulin signaling and, consequently, may contribute to the pathogenesis of insulin resistance. |
| 1296 | 12783777 | High glucose-mediated effects on endothelial cell proliferation occur via p38 MAP kinase. |
| 1297 | 12783777 | The roles of p38 and p42/44 MAP kinases in the high glucose-induced growth effects were determined by assessment of phosphorylated MAP kinases and their downstream activators by Western blot and by pharmacological inhibition of these MAP kinases. |
| 1298 | 12783777 | High glucose increased the activity of total and phosphorylated p38 MAP kinase (P < 0.001) and p42/44 MAP kinase (P < 0.001). |
| 1299 | 12783777 | Coexposure of p38 MAP kinase blocker with high glucose reversed the antiproliferative but not the hypertrophic effects associated with high-glucose conditions. |
| 1300 | 12783777 | Transforming growth factor (TGF)-beta1 increased the levels of phosphorylated p38 MAP kinase, and p38 MAP kinase blockade reversed the antiproliferative effects of this cytokine. |
| 1301 | 12783777 | The high glucose-induced increase in phosphorylated p38 MAP kinase was reversed in the presence of TGF-beta1 neutralizing antibody. |
| 1302 | 12783777 | Although hyperosmolarity also induced antiproliferation (P < 0.0001) and cell hypertrophy (P < 0.05), there was no change in p38 activity, and therefore inhibition of p38 MAP kinase had no influence on these growth responses. |
| 1303 | 12783777 | Blockade of p42/44 MAP kinase had no effect on the changes in endothelial cell growth induced by either high glucose or hyperosmolarity. |
| 1304 | 12783777 | High glucose increased p42/44 and p38 MAP kinase activity in human endothelial cells, but only p38 MAP kinase mediated the antiproliferative growth response through the effects of autocrine TGF-beta1. |
| 1305 | 12951641 | A number of intracellular responses are elicited by C-peptide, including a rise in Ca2+ concentration and activation of MAP-kinase signaling pathways. |
| 1306 | 14515181 | Induction of plasminogen activator inhibitor I by the PPARalpha ligand, Wy-14,643, is dependent on ERK1/2 signaling pathway. |
| 1307 | 14515181 | Impairment of the fibrinolytic system, mostly due to elevated plasma levels of plasminogen activator inhibitor 1 (PAI-1), is often associated with metabolic disorders such as diabetes mellitus and insulin-resistance syndrome. |
| 1308 | 14515181 | Moreover, insulin, as we have previously shown, directly stimulates PAI-1 production with a mechanism underlying a complex signaling network which ultimately leads to ERK activation. |
| 1309 | 14515181 | In this study we have analyzed the effects of agonists of the peroxisome proliferator-activated receptor (PPAR) alpha and gamma on PAI-1 biosynthesis in HepG2 cells in the presence or absence of insulin. |
| 1310 | 14515181 | The high affinity PPARalpha agonist, Wy-14,643, increased basal and insulin-stimulated PAI-1 antigen release with a mechanism involving gene transcription. |
| 1311 | 14515181 | We then investigated whether the MAP kinase pathway also plays a role in the stimulatory properties of Wy-L4,643. |
| 1312 | 14515181 | Wy-L4,643 increases phosphorylation of ERK and p38 in a time-dependent manner without affecting that of SAPK/JNK or ERK5. |
| 1313 | 14515181 | Moreover, the MEK (ERK kinase) inhibitors, PD98059 and UO126, completely prevented PAI-1 induction by Wy-14,643 without inhibiting the activation of a reporter gene carrying the PPRE element. |
| 1314 | 14515181 | Interestingly, the addition of p38 inhibitor followed by insulin and Wy-14,643 resulted in a greater than additive stimulation of PAI-1 secretion acting through ERK1/2 phosphorylation. |
| 1315 | 14515181 | In contrast, the synthetic PPARgamma agonist, rosiglitazone, did not change PAI-1 level, although this compound induced transcription from the PPRE-driven luciferase reporter construct. |
| 1316 | 14515181 | In conclusion, Wy-14,643 induces PAI-1 gene expression, in the presence or absence of insulin, with a mechanism which is independent on PPARalpha activation and requires signaling through the ERK1/2 signaling pathway. |
| 1317 | 14566971 | Age-related differences in MAP kinase activity in VSMC in response to glucose or TNF-alpha. |
| 1318 | 14566971 | Activator protein-1 (AP-1) binding to DNA increased more in VSMC from old versus young rats (P < 0.02) and was related to increased expression of its components, c-Fos, Fra-1, and JunD. |
| 1319 | 14566971 | The relationship to upstream signals, i.e., activities of mitogen-activated protein kinases (MAPK), was studied using antibodies to total and phosphorylated forms of extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK) and p38. |
| 1320 | 14566971 | High glucose and TNF-alpha increased ERK phosphorylation more in old (P < 0.05); whereas only TNF-alpha induced JNK activation in young (P < 0.04). |
| 1321 | 14566971 | PD98059, a MEK inhibitor, attenuated AP-1 activation, lowered c-Fos and Fra-1 protein levels and reduced cell number and cells positive for proliferating cell nuclear antigen in old. |
| 1322 | 14578290 | Parathyroid hormone-related protein induces insulin expression through activation of MAP kinase-specific phosphatase-1 that dephosphorylates c-Jun NH2-terminal kinase in pancreatic beta-cells. |
| 1323 | 14578290 | Parathyroid hormone-related protein (PTHrP) increases the content and mRNA level of insulin in a mouse beta-cell line, MIN6, and primary-cultured mouse islets. |
| 1324 | 14578290 | We examined the mechanism of PTHrP-induced insulin expression. |
| 1325 | 14578290 | The PTHrP effect was markedly augmented by SB203580, a mitogen-activated protein (MAP) kinase inhibitor, and SB203580 itself increased insulin expression extensively, even without PTHrP. |
| 1326 | 14578290 | Because SB203580 inhibits both p38 and c-jun NH(2)-terminal kinases (JNKs), we investigated the JNK-specific inhibitor SP600125. |
| 1327 | 14578290 | PTHrP induced dephosphorylation of JNK1/2, and PTHrP-induced insulin expression was blocked by a dominant-negative type JNK-APF. |
| 1328 | 14578290 | We suspected that dual specificity MAP kinase phosphatases (MKPs) may be involved in the PTHrP-induced insulin expression by inactivating JNK1/2. |
| 1329 | 14578290 | MIN6 cells contained at least five MKPs, among which only MKP-1 was inducible by PTHrP. |
| 1330 | 14578290 | PTHrP-induced insulin expression was blocked by the MKP-1 expression inhibitor Ro-31-8220, indicating that the PTHrP effect is mediated by MKP-1. |
| 1331 | 14578290 | Indeed, adenoviral MKP-1 expression increased insulin expression by decreasing a phosphorylation form of JNKs and a resulting phosphorylated form of c-jun in MIN6 cells. |
| 1332 | 14578290 | The phosphorylated form of c-jun is known to repress cAMP-dependent insulin gene promoter activity. |
| 1333 | 14578290 | Thus, MKP-1 controls the insulin expression by downregulating a JNK/c-jun pathway. |
| 1334 | 14578290 | Parathyroid hormone-related protein induces insulin expression through activation of MAP kinase-specific phosphatase-1 that dephosphorylates c-Jun NH2-terminal kinase in pancreatic beta-cells. |
| 1335 | 14578290 | Parathyroid hormone-related protein (PTHrP) increases the content and mRNA level of insulin in a mouse beta-cell line, MIN6, and primary-cultured mouse islets. |
| 1336 | 14578290 | We examined the mechanism of PTHrP-induced insulin expression. |
| 1337 | 14578290 | The PTHrP effect was markedly augmented by SB203580, a mitogen-activated protein (MAP) kinase inhibitor, and SB203580 itself increased insulin expression extensively, even without PTHrP. |
| 1338 | 14578290 | Because SB203580 inhibits both p38 and c-jun NH(2)-terminal kinases (JNKs), we investigated the JNK-specific inhibitor SP600125. |
| 1339 | 14578290 | PTHrP induced dephosphorylation of JNK1/2, and PTHrP-induced insulin expression was blocked by a dominant-negative type JNK-APF. |
| 1340 | 14578290 | We suspected that dual specificity MAP kinase phosphatases (MKPs) may be involved in the PTHrP-induced insulin expression by inactivating JNK1/2. |
| 1341 | 14578290 | MIN6 cells contained at least five MKPs, among which only MKP-1 was inducible by PTHrP. |
| 1342 | 14578290 | PTHrP-induced insulin expression was blocked by the MKP-1 expression inhibitor Ro-31-8220, indicating that the PTHrP effect is mediated by MKP-1. |
| 1343 | 14578290 | Indeed, adenoviral MKP-1 expression increased insulin expression by decreasing a phosphorylation form of JNKs and a resulting phosphorylated form of c-jun in MIN6 cells. |
| 1344 | 14578290 | The phosphorylated form of c-jun is known to repress cAMP-dependent insulin gene promoter activity. |
| 1345 | 14578290 | Thus, MKP-1 controls the insulin expression by downregulating a JNK/c-jun pathway. |
| 1346 | 14578290 | Parathyroid hormone-related protein induces insulin expression through activation of MAP kinase-specific phosphatase-1 that dephosphorylates c-Jun NH2-terminal kinase in pancreatic beta-cells. |
| 1347 | 14578290 | Parathyroid hormone-related protein (PTHrP) increases the content and mRNA level of insulin in a mouse beta-cell line, MIN6, and primary-cultured mouse islets. |
| 1348 | 14578290 | We examined the mechanism of PTHrP-induced insulin expression. |
| 1349 | 14578290 | The PTHrP effect was markedly augmented by SB203580, a mitogen-activated protein (MAP) kinase inhibitor, and SB203580 itself increased insulin expression extensively, even without PTHrP. |
| 1350 | 14578290 | Because SB203580 inhibits both p38 and c-jun NH(2)-terminal kinases (JNKs), we investigated the JNK-specific inhibitor SP600125. |
| 1351 | 14578290 | PTHrP induced dephosphorylation of JNK1/2, and PTHrP-induced insulin expression was blocked by a dominant-negative type JNK-APF. |
| 1352 | 14578290 | We suspected that dual specificity MAP kinase phosphatases (MKPs) may be involved in the PTHrP-induced insulin expression by inactivating JNK1/2. |
| 1353 | 14578290 | MIN6 cells contained at least five MKPs, among which only MKP-1 was inducible by PTHrP. |
| 1354 | 14578290 | PTHrP-induced insulin expression was blocked by the MKP-1 expression inhibitor Ro-31-8220, indicating that the PTHrP effect is mediated by MKP-1. |
| 1355 | 14578290 | Indeed, adenoviral MKP-1 expression increased insulin expression by decreasing a phosphorylation form of JNKs and a resulting phosphorylated form of c-jun in MIN6 cells. |
| 1356 | 14578290 | The phosphorylated form of c-jun is known to repress cAMP-dependent insulin gene promoter activity. |
| 1357 | 14578290 | Thus, MKP-1 controls the insulin expression by downregulating a JNK/c-jun pathway. |
| 1358 | 14593614 | The two main transduction pathways are the phosphatidylinositol 3 kinase pathway activating protein kinase B which is involved in priority in metabolic effects, and the MAP kinase pathway involved in nuclear effects, proliferation and differentiation. |
| 1359 | 14593614 | This phosphorylation is activated in response to different signals involved in insulin resistance, hyperinsulinism, TNFalpha or increased free fatty acids from adipose tissue, which are transformed inside the cell in acyl-CoA. |
| 1360 | 14656894 | MEK1,2 response element mediates angiotensin II-stimulated plasminogen activator inhibitor-1 promoter activation. |
| 1361 | 14656894 | The MEK1,2 (MAPK/ERK kinase 1 and 2) pathway mediates the up-regulation of plasminogen activator inhibitor-1 (PAI-1) expression in vascular smooth muscle cells by a variety of hormones, including angiotensin II. |
| 1362 | 14656894 | Transfection of constitutively active MEKK-1, an upstream activator of the mitogen-activated protein (MAP) kinase pathways, was used to isolate an enhancer element located between -89 and -50 bp in PAI-1 promoter that was activated by MEKK-1 and selectively blocked by the MEK1,2 inhibitor PD98059. |
| 1363 | 14656894 | Mutational analysis revealed that the MEKK-1 response element (MRE) contained 2 cis-acting Sp1- and AP-1-like sequences, located between -75 to -70 and -63 to -52 bp, respectively. |
| 1364 | 14656894 | Overexpression of Sp1 enhanced MEKK-1-induced MRE promoter activity and a dominant-negative c-Fos blocked this Sp1 response. |
| 1365 | 14656894 | The combination of Sp1 and c-Jun or c-Fos was required to activate this MRE. |
| 1366 | 14656894 | Angiotensin II (Ang II) stimulation increased c-Fos, c-Jun, and Sp1 binding to the MRE by 100-, 4.9-, and 1.9-fold, respectively, and these responses were inhibited by PD98059 and AT1 receptor antagonist candesartan. |
| 1367 | 14656894 | Intravenous Ang II infusion in rats increased aortic c-Fos binding to the MRE. |
| 1368 | 14656894 | This MRE sequence mediated a 4-fold increase of MEK1,2-dependent PAI-1/luciferase mRNA expression by angiotensin II stimulation. |
| 1369 | 14656894 | This report identifies the MEK1,2 response element that mediates angiotensin II-stimulated PAI-1 promoter activation and shows that activation of this element requires Sp1 and AP-1 co-activation. |
| 1370 | 14664808 | In contrast, both NGF and phosphorylation of trkA increased significantly in DRGs, with a marginal appearance of phosphorylated trkA in axons. |
| 1371 | 14664808 | We suggest that this NGF-independent MAP kinase activation is involved in nonsprouting functions of Neotrofin such as neuroprotection. |
| 1372 | 14737836 | One of the intracellular signal transduction of insulin receptor; MAP kinase may be concerned atherosclerotic mechanisms of insulin resistance. |
| 1373 | 14766203 | Adiponectin suppresses proliferation and superoxide generation and enhances eNOS activity in endothelial cells treated with oxidized LDL. |
| 1374 | 14766203 | Adiponectin (also known as 30-kDa adipocyte complement-related protein or Acrp30) is an abundant adipocyte-derived plasma protein with anti-atherosclerotic and insulin-sensitizing properties. |
| 1375 | 14766203 | Cell treatment with gAd also inhibited basal and oxLDL-induced superoxide release, and suppressed the activation of p42/p44 MAP kinase by oxLDL. |
| 1376 | 15010862 | Normal p21Ras/MAP kinase pathway expression and function in PBMC from patients with polycystic ovary disease. |
| 1377 | 15010862 | The p21Ras/MAP kinase is a major intracellular signaling pathway mediating insulin signaling in insulin responsive tissues. |
| 1378 | 15010862 | The expression, regulation and function of the p21Ras/MAP kinase pathway in PCOD patients were examined. |
| 1379 | 15010862 | The expression of p21Ras and its regulatory proteins; hSOS1 and p120GAP were studied. |
| 1380 | 15010862 | The basal and phytohemaglutinin (PHA) or insulin stimulated phosphorylation of MAP kinase was determined. |
| 1381 | 15010862 | Expression of p21Ras, and its regulatory proteins hSOS1 and p120GAP were similar in PCOD patients and controls. |
| 1382 | 15010862 | Basal, PHA and insulin stimulated phosphorylation of MAP kinase, were also comparable in the two groups as well as their PBMC proliferative response. |
| 1383 | 15010862 | These data indicate that the expression and overall function of the p21Ras/MAP kinase pathway remain intact in non-diabetic patients with PCOD. |
| 1384 | 15010862 | Normal p21Ras/MAP kinase pathway expression and function in PBMC from patients with polycystic ovary disease. |
| 1385 | 15010862 | The p21Ras/MAP kinase is a major intracellular signaling pathway mediating insulin signaling in insulin responsive tissues. |
| 1386 | 15010862 | The expression, regulation and function of the p21Ras/MAP kinase pathway in PCOD patients were examined. |
| 1387 | 15010862 | The expression of p21Ras and its regulatory proteins; hSOS1 and p120GAP were studied. |
| 1388 | 15010862 | The basal and phytohemaglutinin (PHA) or insulin stimulated phosphorylation of MAP kinase was determined. |
| 1389 | 15010862 | Expression of p21Ras, and its regulatory proteins hSOS1 and p120GAP were similar in PCOD patients and controls. |
| 1390 | 15010862 | Basal, PHA and insulin stimulated phosphorylation of MAP kinase, were also comparable in the two groups as well as their PBMC proliferative response. |
| 1391 | 15010862 | These data indicate that the expression and overall function of the p21Ras/MAP kinase pathway remain intact in non-diabetic patients with PCOD. |
| 1392 | 15010862 | Normal p21Ras/MAP kinase pathway expression and function in PBMC from patients with polycystic ovary disease. |
| 1393 | 15010862 | The p21Ras/MAP kinase is a major intracellular signaling pathway mediating insulin signaling in insulin responsive tissues. |
| 1394 | 15010862 | The expression, regulation and function of the p21Ras/MAP kinase pathway in PCOD patients were examined. |
| 1395 | 15010862 | The expression of p21Ras and its regulatory proteins; hSOS1 and p120GAP were studied. |
| 1396 | 15010862 | The basal and phytohemaglutinin (PHA) or insulin stimulated phosphorylation of MAP kinase was determined. |
| 1397 | 15010862 | Expression of p21Ras, and its regulatory proteins hSOS1 and p120GAP were similar in PCOD patients and controls. |
| 1398 | 15010862 | Basal, PHA and insulin stimulated phosphorylation of MAP kinase, were also comparable in the two groups as well as their PBMC proliferative response. |
| 1399 | 15010862 | These data indicate that the expression and overall function of the p21Ras/MAP kinase pathway remain intact in non-diabetic patients with PCOD. |
| 1400 | 15010862 | Normal p21Ras/MAP kinase pathway expression and function in PBMC from patients with polycystic ovary disease. |
| 1401 | 15010862 | The p21Ras/MAP kinase is a major intracellular signaling pathway mediating insulin signaling in insulin responsive tissues. |
| 1402 | 15010862 | The expression, regulation and function of the p21Ras/MAP kinase pathway in PCOD patients were examined. |
| 1403 | 15010862 | The expression of p21Ras and its regulatory proteins; hSOS1 and p120GAP were studied. |
| 1404 | 15010862 | The basal and phytohemaglutinin (PHA) or insulin stimulated phosphorylation of MAP kinase was determined. |
| 1405 | 15010862 | Expression of p21Ras, and its regulatory proteins hSOS1 and p120GAP were similar in PCOD patients and controls. |
| 1406 | 15010862 | Basal, PHA and insulin stimulated phosphorylation of MAP kinase, were also comparable in the two groups as well as their PBMC proliferative response. |
| 1407 | 15010862 | These data indicate that the expression and overall function of the p21Ras/MAP kinase pathway remain intact in non-diabetic patients with PCOD. |
| 1408 | 15010862 | Normal p21Ras/MAP kinase pathway expression and function in PBMC from patients with polycystic ovary disease. |
| 1409 | 15010862 | The p21Ras/MAP kinase is a major intracellular signaling pathway mediating insulin signaling in insulin responsive tissues. |
| 1410 | 15010862 | The expression, regulation and function of the p21Ras/MAP kinase pathway in PCOD patients were examined. |
| 1411 | 15010862 | The expression of p21Ras and its regulatory proteins; hSOS1 and p120GAP were studied. |
| 1412 | 15010862 | The basal and phytohemaglutinin (PHA) or insulin stimulated phosphorylation of MAP kinase was determined. |
| 1413 | 15010862 | Expression of p21Ras, and its regulatory proteins hSOS1 and p120GAP were similar in PCOD patients and controls. |
| 1414 | 15010862 | Basal, PHA and insulin stimulated phosphorylation of MAP kinase, were also comparable in the two groups as well as their PBMC proliferative response. |
| 1415 | 15010862 | These data indicate that the expression and overall function of the p21Ras/MAP kinase pathway remain intact in non-diabetic patients with PCOD. |
| 1416 | 15010862 | Normal p21Ras/MAP kinase pathway expression and function in PBMC from patients with polycystic ovary disease. |
| 1417 | 15010862 | The p21Ras/MAP kinase is a major intracellular signaling pathway mediating insulin signaling in insulin responsive tissues. |
| 1418 | 15010862 | The expression, regulation and function of the p21Ras/MAP kinase pathway in PCOD patients were examined. |
| 1419 | 15010862 | The expression of p21Ras and its regulatory proteins; hSOS1 and p120GAP were studied. |
| 1420 | 15010862 | The basal and phytohemaglutinin (PHA) or insulin stimulated phosphorylation of MAP kinase was determined. |
| 1421 | 15010862 | Expression of p21Ras, and its regulatory proteins hSOS1 and p120GAP were similar in PCOD patients and controls. |
| 1422 | 15010862 | Basal, PHA and insulin stimulated phosphorylation of MAP kinase, were also comparable in the two groups as well as their PBMC proliferative response. |
| 1423 | 15010862 | These data indicate that the expression and overall function of the p21Ras/MAP kinase pathway remain intact in non-diabetic patients with PCOD. |
| 1424 | 15026088 | In parallel, E(2)-dependent MAP-kinase-kinase activity was blocked in the presence of high glucose. |
| 1425 | 15026088 | High glucose also prevented E(2)-induced MAP-kinase-kinase activity. |
| 1426 | 15026088 | Hence, high glucose blocks several effects of E(2) on vascular cell growth, which are mediated, in part, via the MAP-kinase system and are likely contributors to E(2)'s anti-atherosclerotic properties. |
| 1427 | 15026088 | Since RAL's estrogen-mimetic effects on human vascular cell growth were independent of MAP-kinase activation and were not affected by hyperglycemia, the potential use of RAL to circumvent the loss of estrogen function induced by hyperglycemia and diabetes in the human vasculature should be further explored. |
| 1428 | 15026088 | In parallel, E(2)-dependent MAP-kinase-kinase activity was blocked in the presence of high glucose. |
| 1429 | 15026088 | High glucose also prevented E(2)-induced MAP-kinase-kinase activity. |
| 1430 | 15026088 | Hence, high glucose blocks several effects of E(2) on vascular cell growth, which are mediated, in part, via the MAP-kinase system and are likely contributors to E(2)'s anti-atherosclerotic properties. |
| 1431 | 15026088 | Since RAL's estrogen-mimetic effects on human vascular cell growth were independent of MAP-kinase activation and were not affected by hyperglycemia, the potential use of RAL to circumvent the loss of estrogen function induced by hyperglycemia and diabetes in the human vasculature should be further explored. |
| 1432 | 15026088 | In parallel, E(2)-dependent MAP-kinase-kinase activity was blocked in the presence of high glucose. |
| 1433 | 15026088 | High glucose also prevented E(2)-induced MAP-kinase-kinase activity. |
| 1434 | 15026088 | Hence, high glucose blocks several effects of E(2) on vascular cell growth, which are mediated, in part, via the MAP-kinase system and are likely contributors to E(2)'s anti-atherosclerotic properties. |
| 1435 | 15026088 | Since RAL's estrogen-mimetic effects on human vascular cell growth were independent of MAP-kinase activation and were not affected by hyperglycemia, the potential use of RAL to circumvent the loss of estrogen function induced by hyperglycemia and diabetes in the human vasculature should be further explored. |
| 1436 | 15026088 | In parallel, E(2)-dependent MAP-kinase-kinase activity was blocked in the presence of high glucose. |
| 1437 | 15026088 | High glucose also prevented E(2)-induced MAP-kinase-kinase activity. |
| 1438 | 15026088 | Hence, high glucose blocks several effects of E(2) on vascular cell growth, which are mediated, in part, via the MAP-kinase system and are likely contributors to E(2)'s anti-atherosclerotic properties. |
| 1439 | 15026088 | Since RAL's estrogen-mimetic effects on human vascular cell growth were independent of MAP-kinase activation and were not affected by hyperglycemia, the potential use of RAL to circumvent the loss of estrogen function induced by hyperglycemia and diabetes in the human vasculature should be further explored. |
| 1440 | 15031777 | The role of oxytocin, protein kinase A, and ERK-related MAP-kinase in the control of porcine ovarian follicle functions. |
| 1441 | 15031777 | The aim of our in vitro experiments was to study the role of oxytocin (OT), cAMP/protein kinase A (PKA), and mitogen-activated protein kinase (ERKs MAP-kinase) in the control of ovarian cell functions as well as the role of PKA and MAPK in mediating OT effects on these processes. |
| 1442 | 15031777 | The whole porcine ovarian follicles were cultured in the presence or absence of OT (1, 10, 100 ng/ml), PKA inhibitor Rp-cAMPS (10 nM), MAP-kinase inhibitor PD98059 (1 microg/ml), or their combination. |
| 1443 | 15031777 | The release of prostaglandins F (PGF) and E (PGE) were determined by RIA, PKA (alpha-cat subunit), the proliferation-associated peptide PCNA and ERK-1, -2 expression in cell lyzates were analysed by Western-blotting. |
| 1444 | 15031777 | OT stimulated the release of PGF and PGE, and accumulation of PKA, ERK-1/-2, and PCNA in cell lysate. |
| 1445 | 15031777 | PD98059 decreased the basal PGF and PGE output, as well as reduced both ERK-1 and ERK-2 accumulation in cell lysates. |
| 1446 | 15031777 | Rp-cAMPS prevented the OT-induced stimulation of PKA, ERK-1, ERK-2, PGF, and PGE, PD98059 did so for PKA, PGF, and PGE. |
| 1447 | 15031777 | The role of oxytocin, protein kinase A, and ERK-related MAP-kinase in the control of porcine ovarian follicle functions. |
| 1448 | 15031777 | The aim of our in vitro experiments was to study the role of oxytocin (OT), cAMP/protein kinase A (PKA), and mitogen-activated protein kinase (ERKs MAP-kinase) in the control of ovarian cell functions as well as the role of PKA and MAPK in mediating OT effects on these processes. |
| 1449 | 15031777 | The whole porcine ovarian follicles were cultured in the presence or absence of OT (1, 10, 100 ng/ml), PKA inhibitor Rp-cAMPS (10 nM), MAP-kinase inhibitor PD98059 (1 microg/ml), or their combination. |
| 1450 | 15031777 | The release of prostaglandins F (PGF) and E (PGE) were determined by RIA, PKA (alpha-cat subunit), the proliferation-associated peptide PCNA and ERK-1, -2 expression in cell lyzates were analysed by Western-blotting. |
| 1451 | 15031777 | OT stimulated the release of PGF and PGE, and accumulation of PKA, ERK-1/-2, and PCNA in cell lysate. |
| 1452 | 15031777 | PD98059 decreased the basal PGF and PGE output, as well as reduced both ERK-1 and ERK-2 accumulation in cell lysates. |
| 1453 | 15031777 | Rp-cAMPS prevented the OT-induced stimulation of PKA, ERK-1, ERK-2, PGF, and PGE, PD98059 did so for PKA, PGF, and PGE. |
| 1454 | 15031777 | The role of oxytocin, protein kinase A, and ERK-related MAP-kinase in the control of porcine ovarian follicle functions. |
| 1455 | 15031777 | The aim of our in vitro experiments was to study the role of oxytocin (OT), cAMP/protein kinase A (PKA), and mitogen-activated protein kinase (ERKs MAP-kinase) in the control of ovarian cell functions as well as the role of PKA and MAPK in mediating OT effects on these processes. |
| 1456 | 15031777 | The whole porcine ovarian follicles were cultured in the presence or absence of OT (1, 10, 100 ng/ml), PKA inhibitor Rp-cAMPS (10 nM), MAP-kinase inhibitor PD98059 (1 microg/ml), or their combination. |
| 1457 | 15031777 | The release of prostaglandins F (PGF) and E (PGE) were determined by RIA, PKA (alpha-cat subunit), the proliferation-associated peptide PCNA and ERK-1, -2 expression in cell lyzates were analysed by Western-blotting. |
| 1458 | 15031777 | OT stimulated the release of PGF and PGE, and accumulation of PKA, ERK-1/-2, and PCNA in cell lysate. |
| 1459 | 15031777 | PD98059 decreased the basal PGF and PGE output, as well as reduced both ERK-1 and ERK-2 accumulation in cell lysates. |
| 1460 | 15031777 | Rp-cAMPS prevented the OT-induced stimulation of PKA, ERK-1, ERK-2, PGF, and PGE, PD98059 did so for PKA, PGF, and PGE. |
| 1461 | 15220210 | Mitogen-activated protein kinase p38 mediates reduced nerve conduction velocity in experimental diabetic neuropathy: interactions with aldose reductase. |
| 1462 | 15220210 | This study examined the role of p38 mitogen-activated protein (MAP) kinase in transducing high glucose into deficits in nerve conduction velocity (NCV) that are characteristic of diabetic neuropathy. p38 activation and NCV were measured in streptozocin-induced diabetic rats treated with a p38 inhibitor, an aldose reductase inhibitor, and insulin. |
| 1463 | 15220210 | Insulin treatment for the last 4 of 12 weeks of diabetes normalized p38 activation. |
| 1464 | 15220210 | Treatment of diabetic animals with a specific inhibitor of p38 (SB 239063), fidarestat, or insulin also prevented reductions in both motor and sensory NCV. |
| 1465 | 15220210 | Insulin and aldose reductase inhibitors can prevent excess polyol pathway flux, and hence these agents may prevent NCV deficits by preventing p38 MAP kinase activation. |
| 1466 | 15233831 | Ca(2+)- and MAP-kinase dependent signalling pathways are activated, resulting in stimulation of Na(+), K(+)-ATPase and endothelial nitric oxide (NO) synthase, two enzyme systems known to be deficient in diabetes. |
| 1467 | 15331199 | The present study investigated vascular endothelial growth factor (VEGF) and its interactions with endothelin (ET) 1 and 3, endothelial, and inducible nitric oxide synthase (eNOS, iNOS) in mediating diabetes induced retinal vascular dysfunction. |
| 1468 | 15331199 | Male Sprague Dawley rats with streptozotocin (STZ) induced diabetes, with or without VEGF receptor signal inhibitor SU5416 treatment (high or low dose) were investigated after 4 weeks of follow-up. |
| 1469 | 15331199 | Diabetic animals showed higher resistivity index (RI), indicative of vasoconstriction with increased ET-1 and ET-3 mRNA expression, whereas eNOS and iNOS mRNA expressions were un-affected. |
| 1470 | 15331199 | SU5416 treatment corrected increased RI via increased iNOS in spite of increased ET-1, ET-3 and VEGF mRNA expression. |
| 1471 | 15331199 | Cell culture (HUVEC) studies indicate that in part, an SU5416 induced iNOS upregulation may be mediated though a MAP kinase signalling pathway. |
| 1472 | 15379552 | Identification of major ERK-related phosphorylation sites in Gab1. |
| 1473 | 15379552 | To address this question in this report we examined extracellular signal-regulated kinases 1/2 (ERK) specific serine/threonine phosphorylation of the entire Gab1 engaged in insulin signaling in more detail in vitro. |
| 1474 | 15379552 | To elucidate the ERK1/2-specific phosphorylation pattern of Gab1, we used phosphopeptide mapping by two-dimensional HPLC analysis. |
| 1475 | 15379552 | Our results demonstrate that ERK1/2 phosphorylate Gab1 at six serine/threonine residues (T312, S381, S454, T476, S581, S597) in consensus motifs for MAP kinase phosphorylation. |
| 1476 | 15379552 | The biological role of identified phosphorylation sites was proven by PI3K and Akt activity in intact cells. |
| 1477 | 15379552 | These data demonstrate that ERK1/2 modulate insulin action via Gab1 by targeting serine and threonine residues beside YXXM motifs. |
| 1478 | 15379552 | Accordingly, insulin signaling is blocked at the level of PI3K. |
| 1479 | 15634339 | Insulin resistance in human adipocytes occurs downstream of IRS1 after surgical cell isolation but at the level of phosphorylation of IRS1 in type 2 diabetes. |
| 1480 | 15634339 | Tyrosine phosphorylation of the insulin receptor and insulin receptor substrate (IRS)1 was insulin sensitive, but protein kinase B (PKB) and downstream metabolic effects exhibited insulin resistance that was reversed by overnight incubation. |
| 1481 | 15634339 | MAP-kinases ERK1/2 and p38 were strongly phosphorylated after surgery, but was dephosphorylated during reversal of insulin resistance. |
| 1482 | 15634339 | Phosphorylation of MAP-kinase was not caused by collagenase treatment during cell isolation and was present also in tissue pieces that were not subjected to cell isolation procedures. |
| 1483 | 15634339 | IRS1, PKB, and downstream metabolic effects, but not insulin-stimulated tyrosine phosphorylation of insulin receptor, exhibited insulin resistance. |
| 1484 | 15634339 | Moreover, we pinpoint the signalling dysregulation in type 2 diabetes to be the insulin-stimulated phosphorylation of IRS1 in human adipocytes. |
| 1485 | 15640073 | [MAP kinase signal pathway in hyperglycemia-induced congenital neural tube defects]. |
| 1486 | 15640073 | Changes in MAPK signaling pathways were detected by western blot analysis using special antibodies directed against phosphorylated forms of extracellular signal regulated kinase (ERK), Jun N-terminal/stress-activated protein kinase (JNK/SAPK). |
| 1487 | 15640073 | Furthermore, activity of RAF-1, an upstream kinase in ERK1/2 signaling cascade, was evaluated by immunoprecipitation assay. |
| 1488 | 15640073 | Under rescuing circumstance,activations of ERK1/2 and RAF-1 were increased, and JNK1/2 were decreased. |
| 1489 | 15640073 | MAP kinase signal pathway plays a very important role in hyperglycemia induced neural tube defects. |
| 1490 | 15640073 | [MAP kinase signal pathway in hyperglycemia-induced congenital neural tube defects]. |
| 1491 | 15640073 | Changes in MAPK signaling pathways were detected by western blot analysis using special antibodies directed against phosphorylated forms of extracellular signal regulated kinase (ERK), Jun N-terminal/stress-activated protein kinase (JNK/SAPK). |
| 1492 | 15640073 | Furthermore, activity of RAF-1, an upstream kinase in ERK1/2 signaling cascade, was evaluated by immunoprecipitation assay. |
| 1493 | 15640073 | Under rescuing circumstance,activations of ERK1/2 and RAF-1 were increased, and JNK1/2 were decreased. |
| 1494 | 15640073 | MAP kinase signal pathway plays a very important role in hyperglycemia induced neural tube defects. |
| 1495 | 15768830 | Mechanistically, caveolins interact with a variety of downstream signaling molecules, including Src-family tyrosine kinases, p42/44 mitogen activated protein (MAP) kinase, and endothelial nitric oxide synthase (eNOS), and hold these signal transducers in the inactive conformation until activation by an appropriate stimulus. |
| 1496 | 15772130 | We find that the Caudal-related homeobox factor PAL-1 can activate hlh-1 in blastomeres that either lack POP-1/TCF or that have down-regulated POP-1/TCF in response to Wnt/MAP kinase signaling. |
| 1497 | 15772130 | The potent myogenic activity of HLH-1 highlights the remarkable developmental plasticity of early C. elegans blastomeres and reveals the evolutionary conservation of MyoD function. |
| 1498 | 15796922 | The adenylate cyclase activator, forskolin, had an anti-apoptotic effect similar to those of GLP-1 and liraglutide indicating that the effect was cAMP-mediated. |
| 1499 | 15796922 | Blocking the PI3 kinase pathway using wortmannin but not the MAP kinase pathways by PD98059 inhibited the effects of liraglutide. |
| 1500 | 15868369 | In contrast, there are noticeable differences between hepatitis C and NASH, in that HCV modulates cellular gene expression and intracellular signal transduction, including the activation of mitogen-activated protein (MAP) kinase and transcription factor activator protein (AP)-1, while such details have not been noted for NASH. |
| 1501 | 16002993 | Ubiquitin-protein ligase Cbl-b negatively regulates high affinity IgE receptor (FcepsilonRI)-mediated degranulation and cytokine gene transcription in mast cells. |
| 1502 | 16002993 | FcepsilonRI-mediated tyrosine phosphorylation of Syk, Gab2, and phospholipase C-gamma1, and activation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAP kinase), and inhibitor of nuclear factor kappaB kinase (IKK), and generation of Rac1 are unaffected in cells overexpressing the truncated Cbl-b in the lipid raft. |
| 1503 | 16002993 | On the other hand, FcepsilonRI-mediated transcriptional activation of nuclear factor of activated T cells (NFAT), and transcription of interleukin-3 (IL-3) and IL-4 mRNA are inhibited by overexpression of the truncated variant of Cbl-b. |
| 1504 | 16002993 | These structural and functional analyses reveal the mechanism underlying the selective inhibition of cellular signaling by the truncated variant of Cbl-b related to insulin-dependent diabetes mellitus. |
| 1505 | 16041601 | No correlation between the p38 MAPK pathway and the contractile dysfunction in diabetic cardiomyocytes: hyperglycaemia-induced signalling and contractile function. |
| 1506 | 16041601 | TGFbeta expression and p38 MAP-kinase (MAPK) activation were measured by Western blotting. |
| 1507 | 16041601 | Glucose (30 mM) caused an increase in formation of radicals, phosphorylation of p38 MAPK, and TGFbeta expression. |
| 1508 | 16041601 | Neither inhibition of p38 MAPK with SB 202190 (1 microM) nor inhibition of reactive oxygen species with vitamin C did alter these measured functional parameters. |
| 1509 | 16112505 | Inhibition of MAP-kinase cascade normalizes the proliferation rate of fibroblasts from patients with Type 1 diabetes and nephropathy. |
| 1510 | 16112505 | Growth factors control cell proliferation through an intracellular mitogen-activated protein (MAP) kinase cascade. |
| 1511 | 16112505 | We have examined the effect of the inhibition of MAP kinase/ERK kinase (MEK), a key point of the MAP kinase cascade, on the proliferation rate of fibroblasts from 40 patients with Type 1 diabetes (20 with and 20 without DN) and from 10 nondiabetic participants. |
| 1512 | 16112505 | In conclusion, the inhibition of MEK normalizes the proliferation rate of fibroblasts from patients with DN, suggesting that the MAP kinase cascade could be involved in this cellular dysfunction. |
| 1513 | 16112505 | Inhibition of MAP-kinase cascade normalizes the proliferation rate of fibroblasts from patients with Type 1 diabetes and nephropathy. |
| 1514 | 16112505 | Growth factors control cell proliferation through an intracellular mitogen-activated protein (MAP) kinase cascade. |
| 1515 | 16112505 | We have examined the effect of the inhibition of MAP kinase/ERK kinase (MEK), a key point of the MAP kinase cascade, on the proliferation rate of fibroblasts from 40 patients with Type 1 diabetes (20 with and 20 without DN) and from 10 nondiabetic participants. |
| 1516 | 16112505 | In conclusion, the inhibition of MEK normalizes the proliferation rate of fibroblasts from patients with DN, suggesting that the MAP kinase cascade could be involved in this cellular dysfunction. |
| 1517 | 16112505 | Inhibition of MAP-kinase cascade normalizes the proliferation rate of fibroblasts from patients with Type 1 diabetes and nephropathy. |
| 1518 | 16112505 | Growth factors control cell proliferation through an intracellular mitogen-activated protein (MAP) kinase cascade. |
| 1519 | 16112505 | We have examined the effect of the inhibition of MAP kinase/ERK kinase (MEK), a key point of the MAP kinase cascade, on the proliferation rate of fibroblasts from 40 patients with Type 1 diabetes (20 with and 20 without DN) and from 10 nondiabetic participants. |
| 1520 | 16112505 | In conclusion, the inhibition of MEK normalizes the proliferation rate of fibroblasts from patients with DN, suggesting that the MAP kinase cascade could be involved in this cellular dysfunction. |
| 1521 | 16112505 | Inhibition of MAP-kinase cascade normalizes the proliferation rate of fibroblasts from patients with Type 1 diabetes and nephropathy. |
| 1522 | 16112505 | Growth factors control cell proliferation through an intracellular mitogen-activated protein (MAP) kinase cascade. |
| 1523 | 16112505 | We have examined the effect of the inhibition of MAP kinase/ERK kinase (MEK), a key point of the MAP kinase cascade, on the proliferation rate of fibroblasts from 40 patients with Type 1 diabetes (20 with and 20 without DN) and from 10 nondiabetic participants. |
| 1524 | 16112505 | In conclusion, the inhibition of MEK normalizes the proliferation rate of fibroblasts from patients with DN, suggesting that the MAP kinase cascade could be involved in this cellular dysfunction. |
| 1525 | 16178743 | Over the past decade, the design and development of a small molecule that selectively inhibits the p38 mitogen activated protein (MAP) kinase has clearly emerged as one of these challenges within the industry. |
| 1526 | 16178743 | This review will focus on the comparison of the x-ray crystal structures and binding models of the most recent p38 inhibitor-enzyme complexes and the identification of the structural elements and interactions that may be important in providing inhibitor potency and selectivity toward the p38 MAP kinase. |
| 1527 | 16186174 | Connective tissue growth factor (CTGF) expression in the brain is a downstream effector of insulin resistance- associated promotion of Alzheimer's disease beta-amyloid neuropathology. |
| 1528 | 16186174 | With this evidence we continued to explore the regulation of CTGF in postmortem AD brain tissue and found that CTGF expression correlated with the progression of AD clinical dementia and amyloid neuritic plaque (NP) neuropathology, but not neurofibrillary tangle (NFT) deposition. |
| 1529 | 16186174 | Consistent with this evidence, we also found that exposure of Tg2576 mice (a model AD-type amyloid neuropathology) to a diabetogenic diet that promotes IR results in a ~2-fold elevation in CTGF steady-state levels in the brain, coincident with a commensurate promotion of AD-type amyloid plaque burden. |
| 1530 | 16186174 | Finally, using in vitro cellular models of amyloid precursor protein (APP)-processing and Abeta generation/clearance, we confirmed that human recombinant (hr)CTGF may increase Abeta1-40 and Abeta1-42 peptide steady-state levels, possibly through a mechanism that involves gamma-secretase activation and decreased insulin-degrading enzyme (IDE) steady-state levels in a MAP kinase (MAPK)/ phosphatidylinositol 3-kinase (PI-3K)/protein kinase-B (AKT)1-dependent manner. |
| 1531 | 16231089 | Numerous studies in animal models established a key role of the C-jun N-terminal kinase (JNK) family (JNK1, JNK2 and JNK3) in numerous pathological conditions, including cancer, cardiac hypertrophy and failure, neurodegenerative disorders, diabetes, arthritis and asthma. |
| 1532 | 16256366 | Active MAP kinase enzymes are not only valuable for basic biomedical research but are also critical for the development of pharmacological inhibitors as therapeutic drugs in the treatment of relevant human diseases. |
| 1533 | 16256366 | We cloned JNK1, p38, and p38-regulated MAP kinase-activated protein kinase-2 into the mammalian expression vector pEBG, and expressed these protein kinases as glutathione S-transferase fusion proteins in human embryonic kidney 293T cells through transient transfection. |
| 1534 | 16256366 | Active MAP kinase enzymes are not only valuable for basic biomedical research but are also critical for the development of pharmacological inhibitors as therapeutic drugs in the treatment of relevant human diseases. |
| 1535 | 16256366 | We cloned JNK1, p38, and p38-regulated MAP kinase-activated protein kinase-2 into the mammalian expression vector pEBG, and expressed these protein kinases as glutathione S-transferase fusion proteins in human embryonic kidney 293T cells through transient transfection. |
| 1536 | 16291965 | Oral administration of sodium tungstate to adult male streptozotocin-diabetic rats for 3 months normalized serum levels of glucose, insulin, luteinizing hormone, and follicle-stimulating hormone. |
| 1537 | 16291965 | Furthermore, the addition of tungstate or insulin to the mTLC-1 cell line from Leydig cell origin increased the phosphorylation states of MAP-kinase and glycogen synthase kinase-3. |
| 1538 | 16291965 | We propose that this improvement is caused by the combined effect of the tungstate-induced normalization of insulin glucose and luteinizing hormone serum levels and a direct action of the effector on Leydig cells through modulation of at least MAP-kinase and glycogen synthase kinase-3 activities. |
| 1539 | 16291965 | Oral administration of sodium tungstate to adult male streptozotocin-diabetic rats for 3 months normalized serum levels of glucose, insulin, luteinizing hormone, and follicle-stimulating hormone. |
| 1540 | 16291965 | Furthermore, the addition of tungstate or insulin to the mTLC-1 cell line from Leydig cell origin increased the phosphorylation states of MAP-kinase and glycogen synthase kinase-3. |
| 1541 | 16291965 | We propose that this improvement is caused by the combined effect of the tungstate-induced normalization of insulin glucose and luteinizing hormone serum levels and a direct action of the effector on Leydig cells through modulation of at least MAP-kinase and glycogen synthase kinase-3 activities. |
| 1542 | 16467130 | On glucose treatment, both p42/p44 mitogen-activated protein (MAP) kinases and the downstream signaling intermediate NF-kappaB were phosphorylated and translocated to the nucleus. |
| 1543 | 16467130 | Pretreatment of cells with MAP kinase and NF-kappaB-specific inhibitors abolished glucose-induced proliferation. |
| 1544 | 16515851 | AGE-receptor expression, MAP-kinase signal transduction and apoptosis were analyzed using PCR, Western blotting and flow cytometry. |
| 1545 | 16515851 | The mRNA expression of the receptors for AGEs and the AGEs-induced activation of p38 and p44/42 MAP-kinases are demonstrable in CD34 cells. |
| 1546 | 16581000 | A report in this issue of Cell Metabolism suggests that starvation functions via a muscarinic acetylcholine receptor to activate MAP kinase signaling in the pharyngeal muscle of C. elegans (You et al., 2006). |
| 1547 | 16598903 | The two main transduction pathways are the phosphatidylinositol 3 kinase pathway activating protein kinase B which is involved in priority in metabolic effects, and the MAP kinase pathway involved in nuclear effects, proliferation and differentiation. |
| 1548 | 16598903 | This phosphorylation is activated in response to different signals involved in insulin resistance, hyperinsulinism, TNFalpha or increased free fatty acids from adipose tissue, which are transformed inside the cell in acyl-CoA. |
| 1549 | 16604064 | In agreement with this notion, cells lacking VHR were found to upregulate p21(Cip-Waf1), whereas they downregulated the expression of genes for cell-cycle regulators, DNA replication, transcription and mRNA processing. |
| 1550 | 16604064 | Loss of VHR also caused a several-fold increase in serum-induced activation of its substrates, the mitogen-activated protein (MAP) kinases Jnk and Erk. |
| 1551 | 16604064 | VHR-induced cell-cycle arrest was dependent on this hyperactivation of Jnk and Erk, and was reversed by Jnk and Erk inhibition or knock-down. |
| 1552 | 16604064 | We conclude that VHR is required for cell-cycle progression as it modulates MAP kinase activation in a cell-cycle phase-dependent manner. |
| 1553 | 16643859 | Cross-talk between angiotensin II and glucagon receptor signaling mediates phosphorylation of mitogen-activated protein kinases ERK 1/2 in rat glomerular mesangial cells. |
| 1554 | 16643859 | We have recently shown that the pancreatic hormone glucagon-induced phosphorylation of mitogen-activated protein (MAP) kinase ERK 1/2 as well as growth and proliferation of rat glomerular mesangial cells (MCs) via activation of cAMP-dependent protein kinase A (PKA)- and phospholipase C (PLC)/Ca2+-mediated signaling pathways. |
| 1555 | 16643859 | Since circulating glucagon and tissue angiotensin II (Ang II) levels are inappropriately elevated in type 2 diabetes, we tested the hypothesis that glucagon induces phosphorylation of ERK 1/2 in MCs by interacting with Ang II receptor signaling. |
| 1556 | 16643859 | Both glucagon and Ang II-induced ERK 1/2 phosphorylation (glucagon: 214+/-14%; Ang II: 174+/-16%; p<0.001 versus control), and these responses were inhibited by the AT1 receptor blocker losartan (glucagon + losartan: 77+/-14%; Ang II + losartan: 84+/-18%; p<0.01 versus glucagon or Ang II) and the AT2 receptor blocker PD 123319 (glucagon + PD: 78+/-7%; Ang II + PD: 87+/-7%; p<0.01 versus glucagon or Ang II). |
| 1557 | 16643859 | Inhibition of cAMP-dependent PKA with H89 (1 microM) or PLC with U73122 (1 microM) also markedly attenuated the phosphorylation of ERK 1/2 induced by glucagon (glucagon + U73122: 109+/-15%; glucagon + H89: 113+/-16%; p<0.01 versus glucagon) or Ang II (Ang II + U73122: 111+/-13%; Ang II + H89: 86+/-10%; p<0.01 versus Ang II). |
| 1558 | 16643859 | Wortmannin (1 microM), a selective PI 3-kinase inhibitor, also blocked glucagon- or Ang II-induced ERK 1/2 phosphorylation. |
| 1559 | 16643859 | These results suggest that AT1 receptor-activated cAMP-dependent PKA, PLC and PI 3-kinase signaling is involved in glucagon-induced MAP kinase ERK 1/2 phosphorylation in MCs. |
| 1560 | 16643859 | The inhibitory effect of PD 123319 on glucagon-induced ERK 1/2 phosphorylation further suggests that AT2 receptors also play a similar role in this response. |
| 1561 | 16643859 | Cross-talk between angiotensin II and glucagon receptor signaling mediates phosphorylation of mitogen-activated protein kinases ERK 1/2 in rat glomerular mesangial cells. |
| 1562 | 16643859 | We have recently shown that the pancreatic hormone glucagon-induced phosphorylation of mitogen-activated protein (MAP) kinase ERK 1/2 as well as growth and proliferation of rat glomerular mesangial cells (MCs) via activation of cAMP-dependent protein kinase A (PKA)- and phospholipase C (PLC)/Ca2+-mediated signaling pathways. |
| 1563 | 16643859 | Since circulating glucagon and tissue angiotensin II (Ang II) levels are inappropriately elevated in type 2 diabetes, we tested the hypothesis that glucagon induces phosphorylation of ERK 1/2 in MCs by interacting with Ang II receptor signaling. |
| 1564 | 16643859 | Both glucagon and Ang II-induced ERK 1/2 phosphorylation (glucagon: 214+/-14%; Ang II: 174+/-16%; p<0.001 versus control), and these responses were inhibited by the AT1 receptor blocker losartan (glucagon + losartan: 77+/-14%; Ang II + losartan: 84+/-18%; p<0.01 versus glucagon or Ang II) and the AT2 receptor blocker PD 123319 (glucagon + PD: 78+/-7%; Ang II + PD: 87+/-7%; p<0.01 versus glucagon or Ang II). |
| 1565 | 16643859 | Inhibition of cAMP-dependent PKA with H89 (1 microM) or PLC with U73122 (1 microM) also markedly attenuated the phosphorylation of ERK 1/2 induced by glucagon (glucagon + U73122: 109+/-15%; glucagon + H89: 113+/-16%; p<0.01 versus glucagon) or Ang II (Ang II + U73122: 111+/-13%; Ang II + H89: 86+/-10%; p<0.01 versus Ang II). |
| 1566 | 16643859 | Wortmannin (1 microM), a selective PI 3-kinase inhibitor, also blocked glucagon- or Ang II-induced ERK 1/2 phosphorylation. |
| 1567 | 16643859 | These results suggest that AT1 receptor-activated cAMP-dependent PKA, PLC and PI 3-kinase signaling is involved in glucagon-induced MAP kinase ERK 1/2 phosphorylation in MCs. |
| 1568 | 16643859 | The inhibitory effect of PD 123319 on glucagon-induced ERK 1/2 phosphorylation further suggests that AT2 receptors also play a similar role in this response. |
| 1569 | 16699725 | MAP4K5 (mitogen-activated protein kinase kinase kinase kinase 5), an early component of MAP kinase signal cascades was shown to activate Jun kinase in mammalian cells. |
| 1570 | 16699725 | The association between SNPs of MAP4K5 and type 2 diabetes (T2DM) was investigated due to the known relationship of the JNK pathway with T2DM. |
| 1571 | 16699725 | Oral glucose tolerance test (OGTT) and insulin release test (IRT) were performed, and blood DNA samples were extracted and genotyped on the MAP4K5 -822G/A site. |
| 1572 | 16723489 | Hepatocyte growth factor induces retinal vascular permeability via MAP-kinase and PI-3 kinase without altering retinal hemodynamics. |
| 1573 | 16806067 | Engagement of RAGE by its ligands triggers activation of key cellular signalling pathways such as the MAP kinase and NF-kappaB pathways. |
| 1574 | 16814733 | Mice lacking MAP kinase phosphatase-1 have enhanced MAP kinase activity and resistance to diet-induced obesity. |
| 1575 | 16814733 | Here we show that mice lacking the nuclear-localized MKP, MKP-1 (mkp-1(-/-)), have enhanced Erk, p38 MAPK and c-Jun NH(2)-terminal kinase (JNK) activities in insulin-responsive tissues as compared with wild-type mice. |
| 1576 | 16814733 | Although JNK promotes insulin resistance, mkp-1(-/-) mice exhibited unimpaired insulin-mediated signaling and glucose homeostasis. |
| 1577 | 16814733 | We reconciled these results by demonstrating that in mkp-1(-/-) mice, JNK activity was increased in the nucleus, but not the cytosol. |
| 1578 | 16814733 | These results suggest that nuclear regulation of the MAPKs by MKP-1 is essential for the management of metabolic homeostasis in a manner that is spatially uncoupled from the cytosolic actions of the MAPKs. |
| 1579 | 16869889 | Activation of activating transcription factor 2 by p38 MAP kinase during apoptosis induced by human amylin in cultured pancreatic beta-cells. |
| 1580 | 16869889 | We previously reported that fibrillogenic human amylin (hA) evokes beta-cell apoptosis through linked activation of Jun N-terminal kinase 1 (JNK 1) and a caspase cascade. |
| 1581 | 16869889 | Here we show that p38 kinase [p38 mitogen-activated protein (MAP) kinase] became activated by hA treatment of cultured beta-cells whereas extracellular signal-regulated kinase (ERK) did not; by contrast, nonfibrillogenic rat amylin (rA) altered neither. |
| 1582 | 16869889 | Pretreatment with the p38 kinase-inhibitor SB203580 decreased hA-induced apoptosis and caspase-3 activation by approximately 30%; as did combined SB203580 and JNK inhibitor I, by about 70%; and the combination of SB203580, the JNK inhibitor I and a caspase-8 inhibitor, by 100%. |
| 1583 | 16869889 | These findings demonstrate the requirement for concurrent activation of the p38 kinase, JNK and caspase-8 pathways. |
| 1584 | 16869889 | We further showed that hA elicits time-dependent activation of activating transcription factor 2 (ATF-2), which was largely suppressed by SB203580, indicating that this activation is catalyzed mainly by p38 kinase. |
| 1585 | 16869889 | Furthermore, hA-induced apoptosis was suppressed by specific antisense ATF-2, and increased phospho-ATF-2 (p-ATF-2) was associated with increased CRE (cAMP-response element) DNA binding and CRE-mediated transcriptional activity, as well as enhancement of c-jun promoter activation. |
| 1586 | 16869889 | These studies establish p38 MAP kinase-mediated activation of ATF-2 as a significant mechanism in hA-evoked beta-cell death, which may serve as a target for pharmaceutical intervention and effective suppression of beta-cell failure in type-2 diabetes. |
| 1587 | 16937364 | The isoform-specific functions of the c-Jun N-terminal Kinases (JNKs): differences revealed by gene targeting. |
| 1588 | 16937364 | The c-Jun N-terminal kinases (JNKs) are members of the mitogen-activated protein kinase (MAPK) family. |
| 1589 | 16937364 | Initial studies on jnk1(-/-) or jnk2(-/-) mice have shown roles for these JNKs in the immune system whereas studies on jnk3(-/-) mice have highlighted roles for JNK3 in the nervous system. |
| 1590 | 16937364 | Further studies have highlighted the contributions of JNK1 and/or JNK2 to a range of biological and pathological processes. |
| 1591 | 16949803 | The c-Jun N-terminal kinases (JNKs) form a subfamily of the mitogen-activated protein kinases (MAPK). |
| 1592 | 16949803 | Therefore, we have investigated the contractility of blood vessels in mice with genetically deleted JNK1, JNK2, JNK3 and JNK2+3 isoforms and their respective wildtypes. |
| 1593 | 17020808 | The beneficial effects of imatinib may be related to inhibition of the pro-apoptotic MAP kinase JNK. |
| 1594 | 17064973 | Advanced glycation end products stimulate osteoblast apoptosis via the MAP kinase and cytosolic apoptotic pathways. |
| 1595 | 17064973 | CML-collagen increased p38 and JNK activity 3.2- and 4.4-fold, respectively. |
| 1596 | 17064973 | Inhibition of p38 and JNK reduced CML-collagen stimulated apoptosis by 45% and 59% and by 90% when used together (P<0.05). |
| 1597 | 17064973 | The predominant apoptotic pathway induced by CML-collagen involved caspase-8 activation of caspase-3 and was independent of NF-kappaB activation. |
| 1598 | 17106060 | Ghrelin has novel vascular actions that mimic PI 3-kinase-dependent actions of insulin to stimulate production of NO from endothelial cells. |
| 1599 | 17106060 | Therefore, we hypothesized that ghrelin activates endothelial nitric oxide synthase (eNOS) in vascular endothelium, resulting in increased production of nitric oxide (NO) using signaling pathways shared in common with the insulin receptor. |
| 1600 | 17106060 | Similar to insulin, ghrelin acutely stimulated increased production of NO in bovine aortic endothelial cells (BAEC) in primary culture (assessed using NO-specific fluorescent dye 4,5-diaminofluorescein) in a time- and dose-dependent manner. |
| 1601 | 17106060 | Production of NO in response to ghrelin (100 nM, 10 min) in human aortic endothelial cells was blocked by pretreatment of cells with NG-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor), wortmannin [phosphatidylinositol (PI) 3-kinase inhibitor], or (D-Lys3)-GHRP-6 (selective antagonist of ghrelin receptor GHSR-1a), as well as by knockdown of GHSR-1a using small-interfering (si) RNA (but not by mitogen/extracellular signal-regulated kinase inhibitor PD-98059). |
| 1602 | 17106060 | Moreover, ghrelin stimulated increased phosphorylation of Akt (Ser473) and eNOS (Akt phosphorylation site Ser1179) that was inhibitable by knockdown of GHSR-1a using siRNA or by pretreatment of cells with wortmannin but not with PD-98059. |
| 1603 | 17106060 | Ghrelin also stimulated phosphorylation of mitogen-activated protein (MAP) kinase in BAEC. |
| 1604 | 17106060 | However, unlike insulin, ghrelin did not stimulate MAP kinase-dependent secretion of the vasoconstrictor endothelin-1 from BAEC. |
| 1605 | 17106060 | We conclude that ghrelin has novel vascular actions to acutely stimulate production of NO in endothelium using a signaling pathway that involves GHSR-1a, PI 3-kinase, Akt, and eNOS. |
| 1606 | 17106060 | Ghrelin has novel vascular actions that mimic PI 3-kinase-dependent actions of insulin to stimulate production of NO from endothelial cells. |
| 1607 | 17106060 | Therefore, we hypothesized that ghrelin activates endothelial nitric oxide synthase (eNOS) in vascular endothelium, resulting in increased production of nitric oxide (NO) using signaling pathways shared in common with the insulin receptor. |
| 1608 | 17106060 | Similar to insulin, ghrelin acutely stimulated increased production of NO in bovine aortic endothelial cells (BAEC) in primary culture (assessed using NO-specific fluorescent dye 4,5-diaminofluorescein) in a time- and dose-dependent manner. |
| 1609 | 17106060 | Production of NO in response to ghrelin (100 nM, 10 min) in human aortic endothelial cells was blocked by pretreatment of cells with NG-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor), wortmannin [phosphatidylinositol (PI) 3-kinase inhibitor], or (D-Lys3)-GHRP-6 (selective antagonist of ghrelin receptor GHSR-1a), as well as by knockdown of GHSR-1a using small-interfering (si) RNA (but not by mitogen/extracellular signal-regulated kinase inhibitor PD-98059). |
| 1610 | 17106060 | Moreover, ghrelin stimulated increased phosphorylation of Akt (Ser473) and eNOS (Akt phosphorylation site Ser1179) that was inhibitable by knockdown of GHSR-1a using siRNA or by pretreatment of cells with wortmannin but not with PD-98059. |
| 1611 | 17106060 | Ghrelin also stimulated phosphorylation of mitogen-activated protein (MAP) kinase in BAEC. |
| 1612 | 17106060 | However, unlike insulin, ghrelin did not stimulate MAP kinase-dependent secretion of the vasoconstrictor endothelin-1 from BAEC. |
| 1613 | 17106060 | We conclude that ghrelin has novel vascular actions to acutely stimulate production of NO in endothelium using a signaling pathway that involves GHSR-1a, PI 3-kinase, Akt, and eNOS. |
| 1614 | 17137336 | As expected, the three major islet hormones (insulin, glucagon, and somatostatin) were detected, as well as various beta-cell enriched secretory products, ion channels, and transcription factors. |
| 1615 | 17137336 | In addition, significant proteome coverage of metabolic enzymes and cellular pathways was observed, including the integrin signaling cascade and the MAP kinase, NF-kappa beta, and JAK/STAT pathways. |
| 1616 | 17229475 | MAP kinase pathways: the first twenty years. |
| 1617 | 17318765 | These altered hemodynamics act independently and in concert with metabolic pathways, to activate intracellular second messengers such as protein kinase C (PKC) and MAP kinase (MAPK), nuclear transcription factors such as nuclear factor-kappaB (NF-kappaB) and various growth factors such as the prosclerotic cytokines, transforming growth factor-beta1 (TGF-beta1), connective tissue growth factor (CTGF) and the angiogenic, permeability enhancing growth factor, vascular endothelial growth factor, VEGF. |
| 1618 | 17556534 | Moreover, by detecting the activation of the phosphatidylinositol 3-kinase and MAP kinase (MAPK) pathways, we found that oleate promoted the activation of extracellular signal-regulated protein kinase-MAPK pathway mainly via GPR40, increased the expression of early growth response gene-1, leading to the anti-lipoapoptotic effect on NIT-1 cells. |
| 1619 | 17574431 | There are two major types of diabetes mellitus: Type 1 diabetes (insulin-dependent diabetes, IDDM or juvenile onset diabetes) and Type 2 diabetes (non-insulin-dependent diabetes, NIDDM or adult-onset). |
| 1620 | 17574431 | Increased PKC activation have been associated with changes in blood flow, basement membrane thickening, extracellular matrix expansion, increases in vascular permeability, abnormal angiogenesis, excessive apoptosis and changes in enzymatic activity alterations such as Na(+)-K(+)-ATPase, cPLA(2), PI3Kinase and MAP kinase. |
| 1621 | 17575262 | Retinol-binding protein-4 attenuates insulin-induced phosphorylation of IRS1 and ERK1/2 in primary human adipocytes. |
| 1622 | 17575262 | Animal models and patients with type 2 diabetes exhibit elevated levels of circulating retinol-binding protein (RBP4), and RBP4 can induce insulin resistance in mice. |
| 1623 | 17575262 | However, little is known about how RBP4 affects insulin signaling. |
| 1624 | 17575262 | RBP4-treated adipocytes exhibited the same molecular defects in insulin signaling, via IRS1 to MAP kinase, as in adipocytes from patients with type 2 diabetes. |
| 1625 | 17575262 | Without affecting autophosphorylation of the insulin receptor, RBP4 blocked the insulin-stimulated phosphorylation of IRS1 at serine (307) [corresponding to serine (302) in the murine sequence] and concomitantly increased the EC50 (from 0.5 to 2 nM) for insulin stimulation of IRS1 phosphorylation at tyrosine. |
| 1626 | 17575262 | The phosphorylation of IRS1 at serine (312) [corresponding to serine (307) in the murine sequence] was not affected in cells from diabetic patients and was also not affected by RBP4. |
| 1627 | 17575262 | The EC50 for insulin stimulation of downstream phosphorylation of MAP kinase ERK1/2 was increased (from 0.2 to 0.8 nM) by RBP4. |
| 1628 | 17575262 | However, the sensitivity to insulin for downstream signaling to control of protein kinase B and glucose uptake was not affected by RBP4. |
| 1629 | 17575262 | When insulin-resistant adipocytes from patients with type 2 diabetes were incubated with antibodies against RBP4, insulin-induced phosphorylation of IRS1 at serine (307) was normalized and the EC50 for insulin stimulation of ERK1/2 phosphorylation was reduced. |
| 1630 | 17575262 | These findings indicate that RBP4 may be released from diabetic adipocytes and act locally to inhibit phosphorylation of IRS1 at serine (307), a phosphorylation site that may integrate nutrient sensing with insulin signaling. |
| 1631 | 17575262 | Retinol-binding protein-4 attenuates insulin-induced phosphorylation of IRS1 and ERK1/2 in primary human adipocytes. |
| 1632 | 17575262 | Animal models and patients with type 2 diabetes exhibit elevated levels of circulating retinol-binding protein (RBP4), and RBP4 can induce insulin resistance in mice. |
| 1633 | 17575262 | However, little is known about how RBP4 affects insulin signaling. |
| 1634 | 17575262 | RBP4-treated adipocytes exhibited the same molecular defects in insulin signaling, via IRS1 to MAP kinase, as in adipocytes from patients with type 2 diabetes. |
| 1635 | 17575262 | Without affecting autophosphorylation of the insulin receptor, RBP4 blocked the insulin-stimulated phosphorylation of IRS1 at serine (307) [corresponding to serine (302) in the murine sequence] and concomitantly increased the EC50 (from 0.5 to 2 nM) for insulin stimulation of IRS1 phosphorylation at tyrosine. |
| 1636 | 17575262 | The phosphorylation of IRS1 at serine (312) [corresponding to serine (307) in the murine sequence] was not affected in cells from diabetic patients and was also not affected by RBP4. |
| 1637 | 17575262 | The EC50 for insulin stimulation of downstream phosphorylation of MAP kinase ERK1/2 was increased (from 0.2 to 0.8 nM) by RBP4. |
| 1638 | 17575262 | However, the sensitivity to insulin for downstream signaling to control of protein kinase B and glucose uptake was not affected by RBP4. |
| 1639 | 17575262 | When insulin-resistant adipocytes from patients with type 2 diabetes were incubated with antibodies against RBP4, insulin-induced phosphorylation of IRS1 at serine (307) was normalized and the EC50 for insulin stimulation of ERK1/2 phosphorylation was reduced. |
| 1640 | 17575262 | These findings indicate that RBP4 may be released from diabetic adipocytes and act locally to inhibit phosphorylation of IRS1 at serine (307), a phosphorylation site that may integrate nutrient sensing with insulin signaling. |
| 1641 | 17578804 | Somatostatin analogues had an effect on cAMP accumulation, chromogranin A secretion and MAP kinase activity in the cell line. |
| 1642 | 17578804 | Treatment of rat pancreatic islets with somatostatin analogues with selective receptor affinity was not sufficient to induce an inhibition of insulin and glucagon secretion. |
| 1643 | 17612521 | To assess the molecular mechanisms involved in the reactivity of the renal artery, the contribution of mitogen-activated protein kinase (MAP kinase) pathway and of L-type voltage gated Ca(2+) channels (in the contractile response to noradrenaline), of nitric oxide (NO) and Ca(2+) activated K(+) channels (in the endothelium-dependent vasodilator response), and of cGMP (in the endothelium-independent vasodilator response) was examined by exposing the arteries to corresponding inhibitors, and by using myograph and patch-clamp techniques, immunoblotting and NO assays. |
| 1644 | 17612521 | Nebivolol influenced the molecular mechanisms involved in renal artery reactivity in diabetic and hypertensive mice: it increased the NO production and endothelial NO synthase (eNOS) protein expression, decreased the expression of proportional, variant protein in L-type calcium channels and Ca(2+) activated K(+) channels, and diminished the MAP kinase activity. |
| 1645 | 17612521 | To assess the molecular mechanisms involved in the reactivity of the renal artery, the contribution of mitogen-activated protein kinase (MAP kinase) pathway and of L-type voltage gated Ca(2+) channels (in the contractile response to noradrenaline), of nitric oxide (NO) and Ca(2+) activated K(+) channels (in the endothelium-dependent vasodilator response), and of cGMP (in the endothelium-independent vasodilator response) was examined by exposing the arteries to corresponding inhibitors, and by using myograph and patch-clamp techniques, immunoblotting and NO assays. |
| 1646 | 17612521 | Nebivolol influenced the molecular mechanisms involved in renal artery reactivity in diabetic and hypertensive mice: it increased the NO production and endothelial NO synthase (eNOS) protein expression, decreased the expression of proportional, variant protein in L-type calcium channels and Ca(2+) activated K(+) channels, and diminished the MAP kinase activity. |
| 1647 | 17647144 | Expression changes of mitogen-activated protein kinase phosphatase-1 (MKP-1) in myocardium of streptozotocin-induced diabetic rats. |
| 1648 | 17647144 | MAP Kinase Phosphatase-1 (MKP-1) is a dual specific phosphatase selective for MAP kinases, and was believed to implicate in the development of cardiac hypertrophy. |
| 1649 | 17647144 | Moreover, we provided first evidence that down-regulation of cardioprotective peptide MKP-1, the MAPK pathway negative regulator, in myocardium of streptozotocin-induced diabetic rats, which may contribute to the deterioration of cardiac function and lead to diabetic cardiomyopathy. |
| 1650 | 17694057 | Among them is Apert syndrome, one of the most severe forms of craniosynostosis, primarily caused by missense mutations leading to amino acid changes S252W or P253R in fibroblast growth factor receptor 2 (FGFR2). |
| 1651 | 17694057 | Restoration of normal FGFR2 signaling is manifested by an alteration of the activity of extracellular signal-regulated kinases 1 and 2 (ERK1/2), implicating the gene encoding ERK and the genes downstream of it in disease expressivity. |
| 1652 | 17694057 | Furthermore, treatment of the mutant mice with U0126, an inhibitor of mitogen-activated protein (MAP) kinase kinase 1 and 2 (MEK1/2) that blocks phosphorylation and activation of ERK1/2, significantly inhibits craniosynostosis. |
| 1653 | 17694057 | These results illustrate a pathogenic role for ERK activation in craniosynostosis resulting from FGFR2 with the S252W substitution and introduce a new concept of small-molecule inhibitor-mediated prevention and therapy for diseases caused by gain-of-function mutations in the human genome. |
| 1654 | 17938539 | Characterization of activation of MAP kinase superfamily in vasculature from diabetic rats. |
| 1655 | 17981625 | Each of these can lead to aberrant cell signalling that affects innate immunity for example, by activating the MAP kinase pathway or inducing activation of transcription factors such as NF-kappaB. |
| 1656 | 17981625 | These complications are frequently associated with increased expression of inflammatory cytokines such as TNF-alpha, IL-1beta and IL-6 and enhanced generation of reactive oxygen species. |
| 1657 | 17991742 | c-Src is required for tropomyosin receptor kinase C (TrkC)-induced activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway. |
| 1658 | 17991742 | TrkC expression leads to the constitutive activation of two major effector pathways, namely the Ras-MAP kinase (MAPK) mitogenic pathway and the phosphatidylinositol 3-kinase (PI3K)-AKT pathway mediating cell survival. |
| 1659 | 17991742 | Here we define some aspects of the molecular mechanisms regulating TrkC-dependent Ras-Erk1/2 and PI3K/Akt activation. |
| 1660 | 17991742 | We show that endogenous TrkC associated with c-Src in human and mouse cancer cells which express TrkC. |
| 1661 | 17991742 | Suppression of c-Src by RNA interference in highly metastatic 4T1 mammary cancer cells, which express endogenous TrkC, resulted in markedly decreased expression of cyclin D1 and suppression of activation of Ras-Erk1/2 and PI3K-Akt. |
| 1662 | 17991742 | Furthermore, in c-Src-deficient SYF cells, TrkC failed to activate the PI3K-Atk pathway, but not the Ras-Erk1/2 pathway. |
| 1663 | 17991742 | Therefore these data indicate that TrkC induces the PI3K-Akt cascade through the activation of c-Src. |
| 1664 | 18204486 | Change in post-translational modifications of histone H3, heat-shock protein-27 and MAP kinase p38 expression by curcumin in streptozotocin-induced type I diabetic nephropathy. |
| 1665 | 18296638 | Overexpression of the dual-specificity phosphatase MKP-4/DUSP-9 protects against stress-induced insulin resistance. |
| 1666 | 18296638 | Insulin resistance, a hallmark of type 2 diabetes and obesity, is associated with increased activity of MAP and stress-activated protein (SAP) kinases, which results in decreased insulin signaling. |
| 1667 | 18296638 | Our goal was to investigate the role of MAP kinase phosphatase-4 (MKP-4) in modulating this process. |
| 1668 | 18296638 | We found that MKP-4 expression is up-regulated during adipocyte and myocyte differentiation in vitro and up-regulated during fasting in white adipose tissue in vivo. |
| 1669 | 18296638 | Overexpression of MKP-4 in 3T3-L1 cells inhibited ERK and JNK phosphorylation and, to a lesser extent, p38MAPK phosphorylation. |
| 1670 | 18296638 | As a result, the phosphorylation of IRS-1 serine 307 induced by anisomycin was abolished, leading to a sensitization of insulin signaling with recovery of insulin-stimulated IRS-1 tyrosine phosphorylation, IRS-1 docking with phosphatidylinositol 3-kinase, and Akt phosphorylation. |
| 1671 | 18296638 | MKP-4 also reversed the effect of TNF-alpha to inhibit insulin signaling; alter IL-6, Glut1 and Glut4 expression; and inhibit insulin-stimulated glucose uptake in 3T3-L1 adipocytes. |
| 1672 | 18296638 | Overexpression of MKP-4 in the liver of ob/ob mice decreased ERK and JNK phosphorylation, leading to a reduction in fed and fasted glycemia, improved glucose intolerance, decreased expression of gluconeogenic and lipogenic genes, and reduced hepatic steatosis. |
| 1673 | 18296638 | Thus, MKP-4 has a protective effect against the development of insulin resistance through its ability to dephosphorylate and inactivate crucial mediators of stress-induced insulin resistance, such as ERK and JNK, and increasing MKP-4 activity might provide a therapy for insulin-resistant disorders. |
| 1674 | 18456735 | Microvessel vascular smooth muscle cells contribute to collagen type I deposition through ERK1/2 MAP kinase, alphavbeta3-integrin, and TGF-beta1 in response to ANG II and high glucose. |
| 1675 | 18456735 | This study determines that vascular smooth muscle cell (VSMC) signaling through extracellular signal-regulated kinase (ERK) 1/2-mitogen-activated protein (MAP) kinase, alphavbeta(3)-integrin, and transforming growth factor (TGF)-beta1 dictates collagen type I network induction in mesenteric resistance arteries (MRA) from type 1 diabetic (streptozotocin) or hypertensive (HT; ANG II) mice. |
| 1676 | 18456735 | Pressure-passive-diameter relationship reduction was associated with increased collagen type I deposition in MRA from HT and diabetic mice compared with control. |
| 1677 | 18456735 | Treatment of HT and diabetic mice with neutralizing TGF-beta1 antibody reduced MRA stiffness and collagen type I deposition. |
| 1678 | 18456735 | Cultured VSMC stimulated with HG or ANG II for 5 min increased ERK1/2-MAP kinase phosphorylation, whereas a 48-h stimulation induced latent TGF-beta1, alphavbeta(3)-integrin, and collagen type 1 release in the conditioned media. |
| 1679 | 18456735 | TGF-beta1 bioactivity and Smad2 phosphorylation were alphavbeta(3)-integrin-dependent, since beta(3)-integrin antibody and alphavbeta(3)-integrin inhibitor (SB-223245, 10 microM) significantly prevented TGF-beta1 bioactivity and Smad2 phosphorylation. |
| 1680 | 18456735 | Pretreatment of VSMC with ERK1/2-MAP kinase inhibitor (U-0126, 1 microM) reduced alphavbeta(3)-integrin, TGF-beta1, and collagen type 1 content. |
| 1681 | 18456735 | Additionally, alphavbeta(3)-integrin antibody, SB-223245, TGF-beta1-small-intefering RNA (siRNA), and Smad2-siRNA (40 nM) prevented collagen type I network formation in response to ANG II and HG. |
| 1682 | 18456735 | Together, these data provide evidence that resistance artery fibrosis in type 1 diabetes and hypertension is a consequence of abnormal collagen type I release by VSMC and involves ERK1/2, alphavbeta(3)-integrin, and TGF-beta1 signaling. |
| 1683 | 18456735 | Microvessel vascular smooth muscle cells contribute to collagen type I deposition through ERK1/2 MAP kinase, alphavbeta3-integrin, and TGF-beta1 in response to ANG II and high glucose. |
| 1684 | 18456735 | This study determines that vascular smooth muscle cell (VSMC) signaling through extracellular signal-regulated kinase (ERK) 1/2-mitogen-activated protein (MAP) kinase, alphavbeta(3)-integrin, and transforming growth factor (TGF)-beta1 dictates collagen type I network induction in mesenteric resistance arteries (MRA) from type 1 diabetic (streptozotocin) or hypertensive (HT; ANG II) mice. |
| 1685 | 18456735 | Pressure-passive-diameter relationship reduction was associated with increased collagen type I deposition in MRA from HT and diabetic mice compared with control. |
| 1686 | 18456735 | Treatment of HT and diabetic mice with neutralizing TGF-beta1 antibody reduced MRA stiffness and collagen type I deposition. |
| 1687 | 18456735 | Cultured VSMC stimulated with HG or ANG II for 5 min increased ERK1/2-MAP kinase phosphorylation, whereas a 48-h stimulation induced latent TGF-beta1, alphavbeta(3)-integrin, and collagen type 1 release in the conditioned media. |
| 1688 | 18456735 | TGF-beta1 bioactivity and Smad2 phosphorylation were alphavbeta(3)-integrin-dependent, since beta(3)-integrin antibody and alphavbeta(3)-integrin inhibitor (SB-223245, 10 microM) significantly prevented TGF-beta1 bioactivity and Smad2 phosphorylation. |
| 1689 | 18456735 | Pretreatment of VSMC with ERK1/2-MAP kinase inhibitor (U-0126, 1 microM) reduced alphavbeta(3)-integrin, TGF-beta1, and collagen type 1 content. |
| 1690 | 18456735 | Additionally, alphavbeta(3)-integrin antibody, SB-223245, TGF-beta1-small-intefering RNA (siRNA), and Smad2-siRNA (40 nM) prevented collagen type I network formation in response to ANG II and HG. |
| 1691 | 18456735 | Together, these data provide evidence that resistance artery fibrosis in type 1 diabetes and hypertension is a consequence of abnormal collagen type I release by VSMC and involves ERK1/2, alphavbeta(3)-integrin, and TGF-beta1 signaling. |
| 1692 | 18456735 | Microvessel vascular smooth muscle cells contribute to collagen type I deposition through ERK1/2 MAP kinase, alphavbeta3-integrin, and TGF-beta1 in response to ANG II and high glucose. |
| 1693 | 18456735 | This study determines that vascular smooth muscle cell (VSMC) signaling through extracellular signal-regulated kinase (ERK) 1/2-mitogen-activated protein (MAP) kinase, alphavbeta(3)-integrin, and transforming growth factor (TGF)-beta1 dictates collagen type I network induction in mesenteric resistance arteries (MRA) from type 1 diabetic (streptozotocin) or hypertensive (HT; ANG II) mice. |
| 1694 | 18456735 | Pressure-passive-diameter relationship reduction was associated with increased collagen type I deposition in MRA from HT and diabetic mice compared with control. |
| 1695 | 18456735 | Treatment of HT and diabetic mice with neutralizing TGF-beta1 antibody reduced MRA stiffness and collagen type I deposition. |
| 1696 | 18456735 | Cultured VSMC stimulated with HG or ANG II for 5 min increased ERK1/2-MAP kinase phosphorylation, whereas a 48-h stimulation induced latent TGF-beta1, alphavbeta(3)-integrin, and collagen type 1 release in the conditioned media. |
| 1697 | 18456735 | TGF-beta1 bioactivity and Smad2 phosphorylation were alphavbeta(3)-integrin-dependent, since beta(3)-integrin antibody and alphavbeta(3)-integrin inhibitor (SB-223245, 10 microM) significantly prevented TGF-beta1 bioactivity and Smad2 phosphorylation. |
| 1698 | 18456735 | Pretreatment of VSMC with ERK1/2-MAP kinase inhibitor (U-0126, 1 microM) reduced alphavbeta(3)-integrin, TGF-beta1, and collagen type 1 content. |
| 1699 | 18456735 | Additionally, alphavbeta(3)-integrin antibody, SB-223245, TGF-beta1-small-intefering RNA (siRNA), and Smad2-siRNA (40 nM) prevented collagen type I network formation in response to ANG II and HG. |
| 1700 | 18456735 | Together, these data provide evidence that resistance artery fibrosis in type 1 diabetes and hypertension is a consequence of abnormal collagen type I release by VSMC and involves ERK1/2, alphavbeta(3)-integrin, and TGF-beta1 signaling. |
| 1701 | 18456735 | Microvessel vascular smooth muscle cells contribute to collagen type I deposition through ERK1/2 MAP kinase, alphavbeta3-integrin, and TGF-beta1 in response to ANG II and high glucose. |
| 1702 | 18456735 | This study determines that vascular smooth muscle cell (VSMC) signaling through extracellular signal-regulated kinase (ERK) 1/2-mitogen-activated protein (MAP) kinase, alphavbeta(3)-integrin, and transforming growth factor (TGF)-beta1 dictates collagen type I network induction in mesenteric resistance arteries (MRA) from type 1 diabetic (streptozotocin) or hypertensive (HT; ANG II) mice. |
| 1703 | 18456735 | Pressure-passive-diameter relationship reduction was associated with increased collagen type I deposition in MRA from HT and diabetic mice compared with control. |
| 1704 | 18456735 | Treatment of HT and diabetic mice with neutralizing TGF-beta1 antibody reduced MRA stiffness and collagen type I deposition. |
| 1705 | 18456735 | Cultured VSMC stimulated with HG or ANG II for 5 min increased ERK1/2-MAP kinase phosphorylation, whereas a 48-h stimulation induced latent TGF-beta1, alphavbeta(3)-integrin, and collagen type 1 release in the conditioned media. |
| 1706 | 18456735 | TGF-beta1 bioactivity and Smad2 phosphorylation were alphavbeta(3)-integrin-dependent, since beta(3)-integrin antibody and alphavbeta(3)-integrin inhibitor (SB-223245, 10 microM) significantly prevented TGF-beta1 bioactivity and Smad2 phosphorylation. |
| 1707 | 18456735 | Pretreatment of VSMC with ERK1/2-MAP kinase inhibitor (U-0126, 1 microM) reduced alphavbeta(3)-integrin, TGF-beta1, and collagen type 1 content. |
| 1708 | 18456735 | Additionally, alphavbeta(3)-integrin antibody, SB-223245, TGF-beta1-small-intefering RNA (siRNA), and Smad2-siRNA (40 nM) prevented collagen type I network formation in response to ANG II and HG. |
| 1709 | 18456735 | Together, these data provide evidence that resistance artery fibrosis in type 1 diabetes and hypertension is a consequence of abnormal collagen type I release by VSMC and involves ERK1/2, alphavbeta(3)-integrin, and TGF-beta1 signaling. |
| 1710 | 18514235 | Ras activation was quantified by Raf-1 binding assay, and the activation of the signaling proteins, Raf-1 and mitogen activated protein (MAP) kinase, by quantifying their gene transcripts (RTPCR) and/or by protein expression (western blot). |
| 1711 | 18514235 | Diabetes increased the gene expression of Ras-Raf-1 downstream signaling protein MAP kinase by over 50%, and that of nuclear transcriptional factor by 25-30%. |
| 1712 | 18514235 | Ras activation was quantified by Raf-1 binding assay, and the activation of the signaling proteins, Raf-1 and mitogen activated protein (MAP) kinase, by quantifying their gene transcripts (RTPCR) and/or by protein expression (western blot). |
| 1713 | 18514235 | Diabetes increased the gene expression of Ras-Raf-1 downstream signaling protein MAP kinase by over 50%, and that of nuclear transcriptional factor by 25-30%. |
| 1714 | 18585815 | Regarding the metabolic signalling, glargine and insulin-induced comparable dose-dependent phosphorylation of insulin receptor, IRS-1, Akt, and GSK3, whereas detemir-induced kinetics were markedly lower in 3T3-L1 adipocytes and L6 myocytes. |
| 1715 | 18585815 | Concerning the mitogenic properties, glargine and insulin-induced comparable dose-dependent phosphorylation of MAP kinase (MAPK) and 5-bromo-2'-deoxyuridine (BrdU) incorporation. |
| 1716 | 18614617 | Most of the known biological actions of angiotensin II can be attributed to AT1 receptors. |
| 1717 | 18614617 | In these rats, angiotensin II caused significantly higher accumulation of inositol trisphosphate (IP3) and phospholipase C (PLC) activation which was sensitive to blockade by AT1 but not to AT2 antagonist. |
| 1718 | 18614617 | Also, angiotensin II-mediated, AT1-dependent MAP kinase, Na-K-ATPase, and Na/H exchanger 3 activation was higher in BSO-treated rats than in control rats. |
| 1719 | 18614617 | Tempol also normalized the angiotensin II-mediated, AT1-dependent IP3 accumulation and PLC, MAP kinase, Na-K-ATPase, and Na/H exchanger 3 stimulation. |
| 1720 | 18614617 | Most of the known biological actions of angiotensin II can be attributed to AT1 receptors. |
| 1721 | 18614617 | In these rats, angiotensin II caused significantly higher accumulation of inositol trisphosphate (IP3) and phospholipase C (PLC) activation which was sensitive to blockade by AT1 but not to AT2 antagonist. |
| 1722 | 18614617 | Also, angiotensin II-mediated, AT1-dependent MAP kinase, Na-K-ATPase, and Na/H exchanger 3 activation was higher in BSO-treated rats than in control rats. |
| 1723 | 18614617 | Tempol also normalized the angiotensin II-mediated, AT1-dependent IP3 accumulation and PLC, MAP kinase, Na-K-ATPase, and Na/H exchanger 3 stimulation. |
| 1724 | 18719589 | Here we demonstrate that whereas some members of the family of bone morphogenetic proteins (BMPs) support white adipocyte differentiation, BMP7 singularly promotes differentiation of brown preadipocytes even in the absence of the normally required hormonal induction cocktail. |
| 1725 | 18719589 | BMP7 activates a full program of brown adipogenesis including induction of early regulators of brown fat fate PRDM16 (PR-domain-containing 16; ref. 4) and PGC-1alpha (peroxisome proliferator-activated receptor-gamma (PPARgamma) coactivator-1alpha; ref. 5), increased expression of the brown-fat-defining marker uncoupling protein 1 (UCP1) and adipogenic transcription factors PPARgamma and CCAAT/enhancer-binding proteins (C/EBPs), and induction of mitochondrial biogenesis via p38 mitogen-activated protein (MAP) kinase-(also known as Mapk14) and PGC-1-dependent pathways. |
| 1726 | 18719589 | Moreover, BMP7 triggers commitment of mesenchymal progenitor cells to a brown adipocyte lineage, and implantation of these cells into nude mice results in development of adipose tissue containing mostly brown adipocytes. |
| 1727 | 18719589 | Bmp7 knockout embryos show a marked paucity of brown fat and an almost complete absence of UCP1. |
| 1728 | 18719589 | These data reveal an important role of BMP7 in promoting brown adipocyte differentiation and thermogenesis in vivo and in vitro, and provide a potential new therapeutic approach for the treatment of obesity. |
| 1729 | 18779652 | Western blotting was performed to assess the activation of MAP kinase system in the cultured RAoSMC. |
| 1730 | 18779652 | The MAP kinase activity was decreased by RNA interference for RAGE. |
| 1731 | 18779652 | From this study it is concluded that AGEs played a key role in RAoSMC proliferation via MAP kinase dependent pathways. |
| 1732 | 18779652 | Activation of vascular smooth muscle cell (VSMC) proliferation by MAP kinase system and increased formation of ROS may be the possible mechanisms of AGEs induced diabetic vasculopathy. |
| 1733 | 18779652 | Western blotting was performed to assess the activation of MAP kinase system in the cultured RAoSMC. |
| 1734 | 18779652 | The MAP kinase activity was decreased by RNA interference for RAGE. |
| 1735 | 18779652 | From this study it is concluded that AGEs played a key role in RAoSMC proliferation via MAP kinase dependent pathways. |
| 1736 | 18779652 | Activation of vascular smooth muscle cell (VSMC) proliferation by MAP kinase system and increased formation of ROS may be the possible mechanisms of AGEs induced diabetic vasculopathy. |
| 1737 | 18779652 | Western blotting was performed to assess the activation of MAP kinase system in the cultured RAoSMC. |
| 1738 | 18779652 | The MAP kinase activity was decreased by RNA interference for RAGE. |
| 1739 | 18779652 | From this study it is concluded that AGEs played a key role in RAoSMC proliferation via MAP kinase dependent pathways. |
| 1740 | 18779652 | Activation of vascular smooth muscle cell (VSMC) proliferation by MAP kinase system and increased formation of ROS may be the possible mechanisms of AGEs induced diabetic vasculopathy. |
| 1741 | 18779652 | Western blotting was performed to assess the activation of MAP kinase system in the cultured RAoSMC. |
| 1742 | 18779652 | The MAP kinase activity was decreased by RNA interference for RAGE. |
| 1743 | 18779652 | From this study it is concluded that AGEs played a key role in RAoSMC proliferation via MAP kinase dependent pathways. |
| 1744 | 18779652 | Activation of vascular smooth muscle cell (VSMC) proliferation by MAP kinase system and increased formation of ROS may be the possible mechanisms of AGEs induced diabetic vasculopathy. |
| 1745 | 18855677 | We present herein an overview of the progress, along with a brief description of applications to two types of DSPs: Cdc25 and MAP kinase phosphatase (MKP) family members. |
| 1746 | 18855677 | In particular, we focus on combined computational and experimental efforts for designing Cdc25B and MKP-1 inhibitors and understanding their mechanisms of interactions with their target proteins. |
| 1747 | 18948074 | MafA is a basic leucine zipper transcription factor expressed within the beta cells of the pancreas and is required to maintain normal glucose homeostasis as it is involved in various aspects of beta cell biology. |
| 1748 | 18948074 | Inhibition of the MAP-kinase JNK mimics the effects of staurosporine on the expression of mafA. |
| 1749 | 18948074 | However, staurosporine, JNK, and calmodulin kinase have different effects on the induction of insulin expression. |
| 1750 | 19133313 | The induction of C/EBPbeta elicited by palmitate was prevented by inhibiting the ERK1/2 MAP kinase pathway or by reducing mitochondrial fatty acid oxidation with an inhibitor of Carnitine Palmitoyl Transferase-1. |
| 1751 | 19133313 | Overexpression of C/EBPbeta mimicked the detrimental effects of palmitate and resulted in a drastic reduction in insulin promoter activity, impairment in the capacity to respond to secretory stimuli and an increase in apoptosis. |
| 1752 | 19273441 | Changes in apoptotic and MAP Kinase signaling pathways were detected by Western blotting analyses. |
| 1753 | 19273441 | The activity of ERK1/2 was dramatically decreased and the activity of JNK1/2 was significantly increased. |
| 1754 | 19273441 | Differentially expressed genes, MAP Kinase, and apoptotic signal pathways play very important roles in hyperglycemia induced neural tube defects. |
| 1755 | 19273441 | Changes in apoptotic and MAP Kinase signaling pathways were detected by Western blotting analyses. |
| 1756 | 19273441 | The activity of ERK1/2 was dramatically decreased and the activity of JNK1/2 was significantly increased. |
| 1757 | 19273441 | Differentially expressed genes, MAP Kinase, and apoptotic signal pathways play very important roles in hyperglycemia induced neural tube defects. |
| 1758 | 19802778 | This effect was, however, not due to an interfering with EGF-signaling, because I(2) and IL did not affect the phosphorylation of EGF-receptors, EGF-induced activation of MAP-kinase (Erk(1/2)), or EGF-induced lamellar actin protrusion. |
| 1759 | 19933999 | Regulation of MAP kinase-directed mitogenic and protein kinase B-mediated signaling by cannabinoid receptor type 1 in skeletal muscle cells. |
| 1760 | 20213272 | TGF-beta stimulates biglycan synthesis via p38 and ERK phosphorylation of the linker region of Smad2. |
| 1761 | 20213272 | Transforming growth factor (TGF)-beta treatment of human vascular smooth-muscle cells increases the expression of biglycan and causes marked elongation of its glycosaminoglycan (GAG) chains. |
| 1762 | 20213272 | TGF-beta-stimulated phosphorylation of p38, ERK, and JNK as well as Smad2 at both its carboxy terminal (phospho-Smad2C) and in the linker region (phospho-Smad2L). |
| 1763 | 20213272 | Pharmacological inhibition of ERK and p38 blocked TGF-beta-mediated GAG elongation and expression of biglycan whereas inhibition of JNK had no effect. |
| 1764 | 20213272 | Inhibition of ERK and p38 but not JNK attenuated the effect of TGF-beta to increase phospho-Smad2L. |
| 1765 | 20213272 | Thus, MAP kinase signaling through ERK and p38 and via phosphorylation of the linker region of Smad2 mediates the effects of TGF-beta on biglycan synthesis in vascular smooth-muscle cells. |
| 1766 | 20630933 | Expression (gene and protein) of Nox4, p22(phox), and p47(phox), but not Nox1 or Nox2, was increased in kidney cortex, but not medulla, from db/db vs. control mice (db/m) (P < 0.05). |
| 1767 | 20630933 | ROS generation, p38 mitogen-activated protein (MAP) kinase phosphorylation, and content of fibronectin and transforming growth factor (TGF)-β1/2 were increased in db/db vs. db/m (P < 0.01). |
| 1768 | 20630933 | Nox4 downregulation by small-interfering RNA and inhibition of Nox4 activity by GK-136901 (Nox1/4 inhibitor) attenuated d-glucose-induced NADPH oxidase-derived ROS generation. |
| 1769 | 20811974 | The MAP kinase signaling cascades: a system of hundreds of components regulates a diverse array of physiological functions. |
| 1770 | 20811974 | Sequential activation of kinases within the mitogen-activated protein (MAP) kinase (MAPK) cascades is a common, and evolutionary-conserved mechanism of signal transduction. |
| 1771 | 20811974 | These are the extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-Terminal kinase (JNK), p38, and ERK5 cascades. |
| 1772 | 20811974 | The MAP kinase signaling cascades: a system of hundreds of components regulates a diverse array of physiological functions. |
| 1773 | 20811974 | Sequential activation of kinases within the mitogen-activated protein (MAP) kinase (MAPK) cascades is a common, and evolutionary-conserved mechanism of signal transduction. |
| 1774 | 20811974 | These are the extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-Terminal kinase (JNK), p38, and ERK5 cascades. |
| 1775 | 21090814 | This approach was used to screen both the c-Jun N-terminal protein kinase Jnk-1 (involved in insulin signaling) and p38α (involved in the formation of TNFα and other cytokines). |
| 1776 | 21090814 | Jnk-1 and p38α both belong to the MAP kinase family, and the allosteric ligands for both targets bind similarly on a ledge of the protein surface exposed by the MAP insertion present in the CMGC family of protein kinases and distant from the active site. |
| 1777 | 21090814 | Medicinal chemistry studies resulted in an improved Jnk-1 ligand able to increase adiponectin secretion in human adipocytes and increase insulin-induced protein kinase PKB phosphorylation in human hepatocytes, in similar fashion to Jnk-1 siRNA and to rosiglitazone treatment. |
| 1778 | 21372692 | Enoxaparin reduces adrenergic contraction of resistance arterioles in aging and in aging associated with diabetes via engagement of MAP kinase pathway. |
| 1779 | 21372692 | The diminishment of contractility is exerted via MAP kinase pathway, and involves reduction of c-fos gene expression and of transcription factor AP-1 protein expression. |
| 1780 | 21372692 | Understanding the signal transduction mechanisms involved in the altered contractility of vascular wall could provide useful information on the development of specific MAP kinase inhibitors with therapeutic benefits and reduced side effects. |
| 1781 | 21372692 | Enoxaparin reduces adrenergic contraction of resistance arterioles in aging and in aging associated with diabetes via engagement of MAP kinase pathway. |
| 1782 | 21372692 | The diminishment of contractility is exerted via MAP kinase pathway, and involves reduction of c-fos gene expression and of transcription factor AP-1 protein expression. |
| 1783 | 21372692 | Understanding the signal transduction mechanisms involved in the altered contractility of vascular wall could provide useful information on the development of specific MAP kinase inhibitors with therapeutic benefits and reduced side effects. |
| 1784 | 21372692 | Enoxaparin reduces adrenergic contraction of resistance arterioles in aging and in aging associated with diabetes via engagement of MAP kinase pathway. |
| 1785 | 21372692 | The diminishment of contractility is exerted via MAP kinase pathway, and involves reduction of c-fos gene expression and of transcription factor AP-1 protein expression. |
| 1786 | 21372692 | Understanding the signal transduction mechanisms involved in the altered contractility of vascular wall could provide useful information on the development of specific MAP kinase inhibitors with therapeutic benefits and reduced side effects. |
| 1787 | 21562305 | Estrogen-related receptor α regulates skeletal myocyte differentiation via modulation of the ERK MAP kinase pathway. |
| 1788 | 21562305 | The transient induction of MAP kinase phosphatase-1 (MKP-1), which mediates ERK dephosphorylation at the onset of myogenesis, was lost in ERRα-/- myocytes and in XCT790-treated C2C12. |
| 1789 | 21562305 | The ERRα-PGC-1α complex activates the Dusp1 gene, which encodes MKP-1, and ERRα occupies the proximal 5' regulatory region during early differentiation in C2C12 myocytes. |
| 1790 | 21562305 | Collectively, these data demonstrate that ERRα is required for normal skeletal myocyte differentiation via modulation of MAP kinase signaling. |
| 1791 | 21562305 | Estrogen-related receptor α regulates skeletal myocyte differentiation via modulation of the ERK MAP kinase pathway. |
| 1792 | 21562305 | The transient induction of MAP kinase phosphatase-1 (MKP-1), which mediates ERK dephosphorylation at the onset of myogenesis, was lost in ERRα-/- myocytes and in XCT790-treated C2C12. |
| 1793 | 21562305 | The ERRα-PGC-1α complex activates the Dusp1 gene, which encodes MKP-1, and ERRα occupies the proximal 5' regulatory region during early differentiation in C2C12 myocytes. |
| 1794 | 21562305 | Collectively, these data demonstrate that ERRα is required for normal skeletal myocyte differentiation via modulation of MAP kinase signaling. |
| 1795 | 21562305 | Estrogen-related receptor α regulates skeletal myocyte differentiation via modulation of the ERK MAP kinase pathway. |
| 1796 | 21562305 | The transient induction of MAP kinase phosphatase-1 (MKP-1), which mediates ERK dephosphorylation at the onset of myogenesis, was lost in ERRα-/- myocytes and in XCT790-treated C2C12. |
| 1797 | 21562305 | The ERRα-PGC-1α complex activates the Dusp1 gene, which encodes MKP-1, and ERRα occupies the proximal 5' regulatory region during early differentiation in C2C12 myocytes. |
| 1798 | 21562305 | Collectively, these data demonstrate that ERRα is required for normal skeletal myocyte differentiation via modulation of MAP kinase signaling. |
| 1799 | 22162761 | C-peptide increases Na,K-ATPase expression via PKC- and MAP kinase-dependent activation of transcription factor ZEB in human renal tubular cells. |
| 1800 | 22529996 | Cardiac myosin binding protein C and MAP-kinase activating death domain-containing gene polymorphisms and diastolic heart failure. |
| 1801 | 22540890 | This tumor growth reduction was accompanied by the enhanced apoptotic cell death and an increase in Bax:Bcl2 ratio. |
| 1802 | 22540890 | The mechanism by which metformin manifests antitumor effects appears to be dependent on the inhibition of nuclear factor kappa B (NFkB) and mTOR signaling pathways. |
| 1803 | 22540890 | Decreased phosphorylation of NFkB inhibitory protein IKBα together with reduced enhancement of NFkB transcriptional target proteins, iNOS/COX-2 were observed. |
| 1804 | 22540890 | In addition, a decrease in the activation of ERK/p38-driven MAP kinase signaling was seen. |
| 1805 | 22540890 | Similarly, AKT signaling activation as assessed by the diminished phosphorylation at Ser473 with a concomitant decrease in mTOR signaling pathway was also noted as phosphorylation of mTOR regulatory proteins p70S6K and 4E-BP-1 was significantly reduced. |
| 1806 | 22540890 | These results suggest that metformin blocks SCC growth by dampening NFkB and mTOR signaling pathways. |
| 1807 | 22720029 | Activation of EGFR/ERBB2 via pathways involving ERK1/2, P38 MAPK, AKT and FOXO enhances recovery of diabetic hearts from ischemia-reperfusion injury. |
| 1808 | 22720029 | This study characterized the effects of diabetes and/or ischemia on epidermal growth factor receptor, EGFR, and/or erbB2 signaling pathways on cardiac function. |
| 1809 | 22720029 | Isolated heart perfusion model of global ischemia was used to study the effect of chronic inhibition or acute activation of EGFR/erbB2 signaling on cardiac function in a rat model of type-1 diabetes. |
| 1810 | 22720029 | Chronic treatment with AG825 or AG1478, selective inhibitors of erbB2 and EGFR respectively, did not affect hyperglycemia but led to an exacerbation whereas acute administration of the EGFR ligand, epidermal growth factor (EGF), led to an improvement in cardiac recovery in diabetic hearts. |
| 1811 | 22720029 | Diabetes led to attenuated dimerization and phosphorylation of cardiac erbB2 and EGFR receptors that was associated with reduced signaling via extracellular-signal-regulated kinase 1/2 (ERK1/2), p38 mitogen activated protein (MAP) kinase and AKT (protein kinase B). |
| 1812 | 22720029 | Ischemia was also associated with reduced cardiac signaling via these molecules whereas EGF-treatment opposed diabetes and/or ischemia induced changes in ERK1/2, p38 MAP kinase, and AKT-FOXO signaling. |
| 1813 | 22720029 | Co-administration of EGF rescued Losartan-mediated reduction in EGFR phosphorylation and significantly improved cardiac recovery more than with either agent alone. |
| 1814 | 22720029 | EGFR/erbB2 signaling is an important cardiac survival pathway whose activation, particularly in diabetes, ischemia or following treatment with drugs that inhibit this cascade, significantly improves cardiac function. |
| 1815 | 22820249 | Profound conformational changes of PED/PEA-15 in ERK2 complex revealed by NMR backbone dynamics. |
| 1816 | 22820249 | PED/PEA-15 is a small, non-catalytic, DED containing protein that is widely expressed in different tissues and highly conserved among mammals. |
| 1817 | 22820249 | PED/PEA-15 has been found to interact with several protein targets in various pathways, including FADD and procaspase-8 (apoptosis), ERK1/2 (cell cycle entry), and PLD1/2 (diabetes). |
| 1818 | 22820249 | In this research, we have studied the PED/PEA-15 in a complex with ERK2, a MAP kinase, using NMR spectroscopic techniques. |
| 1819 | 22820249 | MAP Kinase signaling pathways are involved in the regulation of many cellular functions, including cell proliferation, differentiation, apoptosis and survival. |
| 1820 | 22820249 | Previous studies have shown that PED/PEA-15 complexes with ERK2 in the cytoplasm and prevents redistribution into the nucleus. |
| 1821 | 22820249 | Here we report NMR chemical shift perturbation and backbone dynamic studies at the fast ps-ns timescale of PED/PEA-15, in its free form and in the complex with ERK2. |
| 1822 | 22820249 | These analyses characterize motions and conformational changes involved in ERK2 recognition and binding that orchestrate the reorganization of the DED and immobilization of the C-terminal tail. |
| 1823 | 22820249 | Profound conformational changes of PED/PEA-15 in ERK2 complex revealed by NMR backbone dynamics. |
| 1824 | 22820249 | PED/PEA-15 is a small, non-catalytic, DED containing protein that is widely expressed in different tissues and highly conserved among mammals. |
| 1825 | 22820249 | PED/PEA-15 has been found to interact with several protein targets in various pathways, including FADD and procaspase-8 (apoptosis), ERK1/2 (cell cycle entry), and PLD1/2 (diabetes). |
| 1826 | 22820249 | In this research, we have studied the PED/PEA-15 in a complex with ERK2, a MAP kinase, using NMR spectroscopic techniques. |
| 1827 | 22820249 | MAP Kinase signaling pathways are involved in the regulation of many cellular functions, including cell proliferation, differentiation, apoptosis and survival. |
| 1828 | 22820249 | Previous studies have shown that PED/PEA-15 complexes with ERK2 in the cytoplasm and prevents redistribution into the nucleus. |
| 1829 | 22820249 | Here we report NMR chemical shift perturbation and backbone dynamic studies at the fast ps-ns timescale of PED/PEA-15, in its free form and in the complex with ERK2. |
| 1830 | 22820249 | These analyses characterize motions and conformational changes involved in ERK2 recognition and binding that orchestrate the reorganization of the DED and immobilization of the C-terminal tail. |
| 1831 | 23056550 | Regulation of the CCL2 gene in pancreatic β-cells by IL-1β and glucocorticoids: role of MKP-1. |
| 1832 | 23056550 | Therefore, we investigated the positive and negative regulatory components controlling expression of the CCL2 gene using isolated rat islets and INS-1-derived β-cell lines. |
| 1833 | 23056550 | We discovered that activation of the CCL2 gene by IL-1β required the p65 subunit of NF-κB and was dependent on genomic response elements located in the -3.6 kb region of the proximal gene promoter. |
| 1834 | 23056550 | CCL2 gene transcription in response to IL-1β was blocked by pharmacological inhibition of the IKKβ and p38 MAPK pathways. |
| 1835 | 23056550 | The IL-1β-mediated increase in CCL2 secretion was also impaired by p38 MAPK inhibition and by glucocorticoids. |
| 1836 | 23056550 | Moreover, multiple synthetic glucocorticoids inhibited the IL-1β-stimulated induction of the CCL2 gene. |
| 1837 | 23056550 | Induction of the MAP Kinase Phosphatase-1 (MKP-1) gene by glucocorticoids or by adenoviral-mediated overexpression decreased p38 MAPK phosphorylation, which diminished CCL2 gene expression, promoter activity, and release of CCL2 protein. |
| 1838 | 23056550 | We conclude that glucocorticoid-mediated repression of IL-1β-induced CCL2 gene transcription and protein secretion occurs in part through the upregulation of the MKP-1 gene and subsequent deactivation of the p38 MAPK. |
| 1839 | 23056550 | Furthermore, the anti-inflammatory actions observed with MKP-1 overexpression were obtained without suppressing glucose-stimulated insulin secretion. |
| 1840 | 23395853 | Retinoids, through activation of retinoic acid receptor (RAR) and retinoid x receptor (RXR), have been linked to control glucose and lipid homeostasis, with effects on obesity and diabetes. |
| 1841 | 23395853 | Diabetic cardiomyopathy was characterized in ZDF rats by increased oxidative stress, apoptosis, fibrosis, inflammation, activation of MAP kinases and NF-κB signaling and diminished Akt phosphorylation, along with decreased glucose transport and increased cardiac lipid accumulation, and ultimately diastolic dysfunction. |
| 1842 | 23395853 | Am580 and LGD1069 attenuated diabetes-induced cardiac dysfunction and the pathological alterations, by improving glucose tolerance and insulin resistance; facilitating Akt activation and glucose utilization, and attenuating oxidative stress and interrelated MAP kinase and NF-κB signaling pathways. |
| 1843 | 23404499 | In investigating the associated mechanisms, we found that leucine itself does not activate the classical Akt- or ERK1/2 MAP kinase-dependent signaling pathways but can facilitate the insulin-induced phosphorylations of Akt(473) and ERK1/2 in a time- and dose-dependent manner in cultured hepatocytes. |
| 1844 | 23404499 | The leucine-facilitated insulin-induced phosphorylation of Akt at residue 473 was not affected by knocking down the key component of mTORC1 or -2 complexes but was blocked by inhibition of c-Src (PP2), PI3K (LY294002), Gαi protein (pertussis toxin or siRNA against Gαi1 gene, or β-arrestin 2 (siRNA)). |
| 1845 | 23404499 | Similarly, the leucine-facilitated insulin activation of ERK1/2 was also blunted by pertussis toxin. |
| 1846 | 23468892 | Obesity-induced insulin resistance in human skeletal muscle is characterised by defective activation of p42/p44 MAP kinase. |
| 1847 | 23468892 | Although IR is closely associated with obesity, the identity of the molecular defect(s) underlying obesity-induced IR in skeletal muscle remains controversial; reduced post-receptor signalling of the insulin receptor substrate 1 (IRS1) adaptor protein and downstream effectors such as protein kinase B (PKB) have previously been implicated. |
| 1848 | 23468892 | The most striking abnormality was significantly reduced insulin-induced activation of p42/44 MAP kinase, measured by specific assay, in the volunteers with poor insulin sensitivity. |
| 1849 | 23468892 | However, there was no relationship between individuals' BMI or M-value and protein expression/phosphorylation of IRS1, PKB, or p42/44 MAP kinase protein, under basal or hyperinsulinaemic conditions. |
| 1850 | 23468892 | In the few individuals with poor insulin sensitivity but preserved p42/44 MAP kinase activation, other signalling defects were evident. |
| 1851 | 23468892 | These findings implicate defective p42/44 MAP kinase signalling as a potential contributor to obesity-related IR in a non-diabetic population, although clearly multiple signalling defects underlie obesity associated IR. |
| 1852 | 23468892 | Obesity-induced insulin resistance in human skeletal muscle is characterised by defective activation of p42/p44 MAP kinase. |
| 1853 | 23468892 | Although IR is closely associated with obesity, the identity of the molecular defect(s) underlying obesity-induced IR in skeletal muscle remains controversial; reduced post-receptor signalling of the insulin receptor substrate 1 (IRS1) adaptor protein and downstream effectors such as protein kinase B (PKB) have previously been implicated. |
| 1854 | 23468892 | The most striking abnormality was significantly reduced insulin-induced activation of p42/44 MAP kinase, measured by specific assay, in the volunteers with poor insulin sensitivity. |
| 1855 | 23468892 | However, there was no relationship between individuals' BMI or M-value and protein expression/phosphorylation of IRS1, PKB, or p42/44 MAP kinase protein, under basal or hyperinsulinaemic conditions. |
| 1856 | 23468892 | In the few individuals with poor insulin sensitivity but preserved p42/44 MAP kinase activation, other signalling defects were evident. |
| 1857 | 23468892 | These findings implicate defective p42/44 MAP kinase signalling as a potential contributor to obesity-related IR in a non-diabetic population, although clearly multiple signalling defects underlie obesity associated IR. |
| 1858 | 23468892 | Obesity-induced insulin resistance in human skeletal muscle is characterised by defective activation of p42/p44 MAP kinase. |
| 1859 | 23468892 | Although IR is closely associated with obesity, the identity of the molecular defect(s) underlying obesity-induced IR in skeletal muscle remains controversial; reduced post-receptor signalling of the insulin receptor substrate 1 (IRS1) adaptor protein and downstream effectors such as protein kinase B (PKB) have previously been implicated. |
| 1860 | 23468892 | The most striking abnormality was significantly reduced insulin-induced activation of p42/44 MAP kinase, measured by specific assay, in the volunteers with poor insulin sensitivity. |
| 1861 | 23468892 | However, there was no relationship between individuals' BMI or M-value and protein expression/phosphorylation of IRS1, PKB, or p42/44 MAP kinase protein, under basal or hyperinsulinaemic conditions. |
| 1862 | 23468892 | In the few individuals with poor insulin sensitivity but preserved p42/44 MAP kinase activation, other signalling defects were evident. |
| 1863 | 23468892 | These findings implicate defective p42/44 MAP kinase signalling as a potential contributor to obesity-related IR in a non-diabetic population, although clearly multiple signalling defects underlie obesity associated IR. |
| 1864 | 23468892 | Obesity-induced insulin resistance in human skeletal muscle is characterised by defective activation of p42/p44 MAP kinase. |
| 1865 | 23468892 | Although IR is closely associated with obesity, the identity of the molecular defect(s) underlying obesity-induced IR in skeletal muscle remains controversial; reduced post-receptor signalling of the insulin receptor substrate 1 (IRS1) adaptor protein and downstream effectors such as protein kinase B (PKB) have previously been implicated. |
| 1866 | 23468892 | The most striking abnormality was significantly reduced insulin-induced activation of p42/44 MAP kinase, measured by specific assay, in the volunteers with poor insulin sensitivity. |
| 1867 | 23468892 | However, there was no relationship between individuals' BMI or M-value and protein expression/phosphorylation of IRS1, PKB, or p42/44 MAP kinase protein, under basal or hyperinsulinaemic conditions. |
| 1868 | 23468892 | In the few individuals with poor insulin sensitivity but preserved p42/44 MAP kinase activation, other signalling defects were evident. |
| 1869 | 23468892 | These findings implicate defective p42/44 MAP kinase signalling as a potential contributor to obesity-related IR in a non-diabetic population, although clearly multiple signalling defects underlie obesity associated IR. |
| 1870 | 23468892 | Obesity-induced insulin resistance in human skeletal muscle is characterised by defective activation of p42/p44 MAP kinase. |
| 1871 | 23468892 | Although IR is closely associated with obesity, the identity of the molecular defect(s) underlying obesity-induced IR in skeletal muscle remains controversial; reduced post-receptor signalling of the insulin receptor substrate 1 (IRS1) adaptor protein and downstream effectors such as protein kinase B (PKB) have previously been implicated. |
| 1872 | 23468892 | The most striking abnormality was significantly reduced insulin-induced activation of p42/44 MAP kinase, measured by specific assay, in the volunteers with poor insulin sensitivity. |
| 1873 | 23468892 | However, there was no relationship between individuals' BMI or M-value and protein expression/phosphorylation of IRS1, PKB, or p42/44 MAP kinase protein, under basal or hyperinsulinaemic conditions. |
| 1874 | 23468892 | In the few individuals with poor insulin sensitivity but preserved p42/44 MAP kinase activation, other signalling defects were evident. |
| 1875 | 23468892 | These findings implicate defective p42/44 MAP kinase signalling as a potential contributor to obesity-related IR in a non-diabetic population, although clearly multiple signalling defects underlie obesity associated IR. |
| 1876 | 23481023 | These effects were associated with a PEA-15-dependent down-regulation of integrin αvβ5 as well as with elevated levels of the phosphorylated MAP kinase ERK1/2. |
| 1877 | 23481023 | Moreover, expression of PEA-15 resulted in significant protection from cell death induced by cytotoxic drugs (5-FU, cisplatin), by the death ligand TRAIL, or by serum withdrawal. |
| 1878 | 23675062 | Inhibition of Raf-1 kinase repressed glucose-induced apoptosis of the cells by 75%, and this was accompanied by attenuation of activation of MAP kinase, ERK-1, nuclear transcriptional factor and caspase-3. |
| 1879 | 23698110 | Inhibition of the TNF-α-induced serine phosphorylation of IRS-1 at 636/639 by AICAR. |
| 1880 | 23698110 | AMP-activated protein kinase (AMPK) contributes to the acceleration of insulin signaling. |
| 1881 | 23698110 | However, the mechanism by which AMPK regulates insulin signaling remains unclear. |
| 1882 | 23698110 | Here we investigated the role of AMPK in serine phosphorylation of IRS-1 at 636/639 and 307, which is induced by tumor necrosis factor (TNF)-α in 3T3L1 adipocytes. |
| 1883 | 23698110 | We demonstrated that the AMPK activator 5-aminoimidazole-4-carboxamide-1-d-ribofuranoside (AICAR) significantly inhibited the TNF-α-induced serine phosphorylation of IRS-1 at 636/639 and 307 by suppression of extracellular signal-regulated kinase (ERK) phosphorylation but not c-Jun-NH2-terminal kinase (JNK) phosphorylation. |
| 1884 | 23698110 | In addition, AICAR stimulation resulted in enhanced interaction between ERK and MAP kinase phosphatase-4 (DUSP9/MKP-4) without affecting DUSP9/MPK4 mRNA synthesis. |
| 1885 | 23698110 | Moreover, intraperitoneal administration (0.25 g/kg) of AICAR to db/db mice improved blood glucose levels and inhibited the phosphorylation of ERK in adipose tissue. |
| 1886 | 23698110 | In conclusion, we propose a new mechanism in which AICAR suppresses TNF-α-induced serine phosphorylation of IRS-1 at 636/639 and 307 by enhancing the interaction between ERK and DUSP9/MKP-4. |
| 1887 | 23716797 | The Role of EGFR/ERK/ELK-1 MAP Kinase Pathway in the Underlying Damage to Diabetic Rat Skin. |
| 1888 | 12975336 | Insulin and glucagon signaling in regulation of microsomal epoxide hydrolase expression in primary cultured rat hepatocytes. |
| 1889 | 12975336 | The phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin or LY294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one], and rapamycin, an inhibitor of p70 S6 kinase phosphorylation, ameliorated the insulin-mediated increase in mEH protein levels. |
| 1890 | 12975336 | The p38 mitogen-activated protein (MAP) kinase inhibitors SB203580 and SB202190 also abrogated the insulin-mediated increase in mEH protein. |
| 1891 | 12975336 | Furthermore, these data suggest that PI3K and p70 S6 kinase are active in the regulation of insulin-mediated mEH expression. |
| 1892 | 12975336 | We also provide data implicating p38 MAP kinase in the insulin-mediated increase in mEH levels. |
| 1893 | 16282221 | The cannabinoid CB1 receptor antagonist rimonabant (SR141716) inhibits cell proliferation and increases markers of adipocyte maturation in cultured mouse 3T3 F442A preadipocytes. |
| 1894 | 16282221 | In parallel to this inhibitory effect on preadipocyte cell proliferation, rimonabant (25-100 nM) stimulates mRNA expression and protein levels of two late markers of adipocyte differentiation (adiponectin and glyceraldehyde-3-phosphate dehydrogenase) with a maximal effect at 100 nM, without inducing the accumulation of lipid droplets. |
| 1895 | 16282221 | Furthermore, treatment of mouse 3T3 F442A preadipocytes with rimonabant (100 nM) inhibits basal and serum-induced p42/44 mitogen-activated protein (MAP) kinase activity. |
| 1896 | 16282221 | These results suggest that inhibition of MAP kinase activity by rimonabant may be one of mechanisms involved in the inhibition of 3T3 F442A preadipocyte cell proliferation and stimulation of adiponectin and GAPDH expression. |
| 1897 | 16282221 | The cannabinoid CB1 receptor antagonist rimonabant (SR141716) inhibits cell proliferation and increases markers of adipocyte maturation in cultured mouse 3T3 F442A preadipocytes. |
| 1898 | 16282221 | In parallel to this inhibitory effect on preadipocyte cell proliferation, rimonabant (25-100 nM) stimulates mRNA expression and protein levels of two late markers of adipocyte differentiation (adiponectin and glyceraldehyde-3-phosphate dehydrogenase) with a maximal effect at 100 nM, without inducing the accumulation of lipid droplets. |
| 1899 | 16282221 | Furthermore, treatment of mouse 3T3 F442A preadipocytes with rimonabant (100 nM) inhibits basal and serum-induced p42/44 mitogen-activated protein (MAP) kinase activity. |
| 1900 | 16282221 | These results suggest that inhibition of MAP kinase activity by rimonabant may be one of mechanisms involved in the inhibition of 3T3 F442A preadipocyte cell proliferation and stimulation of adiponectin and GAPDH expression. |