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Gene Information
Gene symbol: RAF1
Gene name: v-raf-1 murine leukemia viral oncogene homolog 1
HGNC ID: 9829
Synonyms: Raf-1, c-Raf, CRAF
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 | 1322500 | Raf-1 activates MAP kinase-kinase. |
| 18 | 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. |
| 19 | 1322500 | The physiological substrates of the protein c-Raf-1 are unknown. |
| 20 | 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). |
| 21 | 1322500 | Here we report that MAPK-K as well as Erk1 and 2 are constitutively active in v-raf-transformed cells. |
| 22 | 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. |
| 23 | 1322500 | These results indicate that c-Raf-1 is an immediate upstream activator of MAPK-K in vivo. |
| 24 | 1322500 | To our knowledge, MAPK-K is the first physiological substrate of the c-raf-1 protooncogene product to be identified. |
| 25 | 1322500 | Raf-1 activates MAP kinase-kinase. |
| 26 | 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. |
| 27 | 1322500 | The physiological substrates of the protein c-Raf-1 are unknown. |
| 28 | 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). |
| 29 | 1322500 | Here we report that MAPK-K as well as Erk1 and 2 are constitutively active in v-raf-transformed cells. |
| 30 | 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. |
| 31 | 1322500 | These results indicate that c-Raf-1 is an immediate upstream activator of MAPK-K in vivo. |
| 32 | 1322500 | To our knowledge, MAPK-K is the first physiological substrate of the c-raf-1 protooncogene product to be identified. |
| 33 | 1322500 | Raf-1 activates MAP kinase-kinase. |
| 34 | 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. |
| 35 | 1322500 | The physiological substrates of the protein c-Raf-1 are unknown. |
| 36 | 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). |
| 37 | 1322500 | Here we report that MAPK-K as well as Erk1 and 2 are constitutively active in v-raf-transformed cells. |
| 38 | 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. |
| 39 | 1322500 | These results indicate that c-Raf-1 is an immediate upstream activator of MAPK-K in vivo. |
| 40 | 1322500 | To our knowledge, MAPK-K is the first physiological substrate of the c-raf-1 protooncogene product to be identified. |
| 41 | 1322500 | Raf-1 activates MAP kinase-kinase. |
| 42 | 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. |
| 43 | 1322500 | The physiological substrates of the protein c-Raf-1 are unknown. |
| 44 | 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). |
| 45 | 1322500 | Here we report that MAPK-K as well as Erk1 and 2 are constitutively active in v-raf-transformed cells. |
| 46 | 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. |
| 47 | 1322500 | These results indicate that c-Raf-1 is an immediate upstream activator of MAPK-K in vivo. |
| 48 | 1322500 | To our knowledge, MAPK-K is the first physiological substrate of the c-raf-1 protooncogene product to be identified. |
| 49 | 3052263 | Mononuclear cells from patients and animals with autoimmune disorders express increased quantities of oncogenes such as c-myc, c-myb and c-raf. |
| 50 | 7559537 | The 14.3.3 zeta protein is a ubiquitous and abundant arachidonate-selective acyltransferase and putative phospholipase A2, which self-assembles into dimers and binds to c-Raf-1 and other polypeptides in vitro and in intact cells. |
| 51 | 7559537 | Moreover, expression of recombinant 14.3.3 zeta in COS cells beyond the substantial level of endogenous 14.3.3 protein does not alter endogenous Raf kinase, as judged by the activity of a cotransfected Erk-1 reporter. |
| 52 | 8340422 | Mitogen regulation of c-Raf-1 protein kinase activity toward mitogen-activated protein kinase-kinase. |
| 53 | 8340422 | The c-raf-1 protooncogene encodes a Ser/Thr protein kinase. |
| 54 | 8340422 | A mitogen-activated protein kinase-kinase (MAPKK) purified from bovine brain is phosphorylated and activated 4-9-fold in vitro by c-Raf-1 from mitogen-treated cells. c-Raf-1 protein kinase activity, measured by the phosphorylation of brain MAPKK substrate, is detectably activated within 1 min after addition of platelet-derived growth factor (PDGF) to 3T3 cells, increasing more rapidly than the endogenous NIH 3T3 cell MAPKK activity. c-Raf-1 activation is also induced by insulin, phorbol ester, thrombin, and endothelin. |
| 55 | 8340422 | PDGF-, epidermal groth factor-, and insulin-stimulated 32P-c-Raf-1 yield very similar, complex tryptic 32P-peptide maps, wherein only 2 of 10 32P-peptides appear entirely de novo after growth factor addition. |
| 56 | 8340422 | Mitogen-activated protein kinase/extracellular signal-regulated kinase-2 can phosphorylate c-Raf-1 in vitro on 4-6 tryptic 32P-peptides, all of which comigrate with tryptic 32P-peptides derived from c-Raf-1 labeled in situ. |
| 57 | 8340422 | Mitogen-activated protein kinase phosphorylation of c-Raf-1 in vitro, however, does not 1) generate 32P-peptides that comigrate with those that appear de novo after PDGF or insulin treatment in situ; 2) does not convert c-Raf-1 polypeptides to a slower mobility on SDS-polyacrylamide gel electrophoresis as is seen after PDGF or insulin; 3) does not alter c-Raf-1 kinase activity toward MAPKK. |
| 58 | 8340422 | Thus, based on overlapping site specificity, Erk-2 is a viable candidate to be among the PDGF-stimulated c-Raf-1 kinases. |
| 59 | 8340422 | Although PDGF/insulin-stimulated c-Raf-1 Ser/Thr phosphorylation may be necessary to sustain the active state, a role for mitogen-activated protein kinase/extracellular signal-regulated kinase-2 phosphorylation in the initiation of c-Raf-1 activation is unlikely. |
| 60 | 8340422 | Mitogen regulation of c-Raf-1 protein kinase activity toward mitogen-activated protein kinase-kinase. |
| 61 | 8340422 | The c-raf-1 protooncogene encodes a Ser/Thr protein kinase. |
| 62 | 8340422 | A mitogen-activated protein kinase-kinase (MAPKK) purified from bovine brain is phosphorylated and activated 4-9-fold in vitro by c-Raf-1 from mitogen-treated cells. c-Raf-1 protein kinase activity, measured by the phosphorylation of brain MAPKK substrate, is detectably activated within 1 min after addition of platelet-derived growth factor (PDGF) to 3T3 cells, increasing more rapidly than the endogenous NIH 3T3 cell MAPKK activity. c-Raf-1 activation is also induced by insulin, phorbol ester, thrombin, and endothelin. |
| 63 | 8340422 | PDGF-, epidermal groth factor-, and insulin-stimulated 32P-c-Raf-1 yield very similar, complex tryptic 32P-peptide maps, wherein only 2 of 10 32P-peptides appear entirely de novo after growth factor addition. |
| 64 | 8340422 | Mitogen-activated protein kinase/extracellular signal-regulated kinase-2 can phosphorylate c-Raf-1 in vitro on 4-6 tryptic 32P-peptides, all of which comigrate with tryptic 32P-peptides derived from c-Raf-1 labeled in situ. |
| 65 | 8340422 | Mitogen-activated protein kinase phosphorylation of c-Raf-1 in vitro, however, does not 1) generate 32P-peptides that comigrate with those that appear de novo after PDGF or insulin treatment in situ; 2) does not convert c-Raf-1 polypeptides to a slower mobility on SDS-polyacrylamide gel electrophoresis as is seen after PDGF or insulin; 3) does not alter c-Raf-1 kinase activity toward MAPKK. |
| 66 | 8340422 | Thus, based on overlapping site specificity, Erk-2 is a viable candidate to be among the PDGF-stimulated c-Raf-1 kinases. |
| 67 | 8340422 | Although PDGF/insulin-stimulated c-Raf-1 Ser/Thr phosphorylation may be necessary to sustain the active state, a role for mitogen-activated protein kinase/extracellular signal-regulated kinase-2 phosphorylation in the initiation of c-Raf-1 activation is unlikely. |
| 68 | 8340422 | Mitogen regulation of c-Raf-1 protein kinase activity toward mitogen-activated protein kinase-kinase. |
| 69 | 8340422 | The c-raf-1 protooncogene encodes a Ser/Thr protein kinase. |
| 70 | 8340422 | A mitogen-activated protein kinase-kinase (MAPKK) purified from bovine brain is phosphorylated and activated 4-9-fold in vitro by c-Raf-1 from mitogen-treated cells. c-Raf-1 protein kinase activity, measured by the phosphorylation of brain MAPKK substrate, is detectably activated within 1 min after addition of platelet-derived growth factor (PDGF) to 3T3 cells, increasing more rapidly than the endogenous NIH 3T3 cell MAPKK activity. c-Raf-1 activation is also induced by insulin, phorbol ester, thrombin, and endothelin. |
| 71 | 8340422 | PDGF-, epidermal groth factor-, and insulin-stimulated 32P-c-Raf-1 yield very similar, complex tryptic 32P-peptide maps, wherein only 2 of 10 32P-peptides appear entirely de novo after growth factor addition. |
| 72 | 8340422 | Mitogen-activated protein kinase/extracellular signal-regulated kinase-2 can phosphorylate c-Raf-1 in vitro on 4-6 tryptic 32P-peptides, all of which comigrate with tryptic 32P-peptides derived from c-Raf-1 labeled in situ. |
| 73 | 8340422 | Mitogen-activated protein kinase phosphorylation of c-Raf-1 in vitro, however, does not 1) generate 32P-peptides that comigrate with those that appear de novo after PDGF or insulin treatment in situ; 2) does not convert c-Raf-1 polypeptides to a slower mobility on SDS-polyacrylamide gel electrophoresis as is seen after PDGF or insulin; 3) does not alter c-Raf-1 kinase activity toward MAPKK. |
| 74 | 8340422 | Thus, based on overlapping site specificity, Erk-2 is a viable candidate to be among the PDGF-stimulated c-Raf-1 kinases. |
| 75 | 8340422 | Although PDGF/insulin-stimulated c-Raf-1 Ser/Thr phosphorylation may be necessary to sustain the active state, a role for mitogen-activated protein kinase/extracellular signal-regulated kinase-2 phosphorylation in the initiation of c-Raf-1 activation is unlikely. |
| 76 | 8340422 | Mitogen regulation of c-Raf-1 protein kinase activity toward mitogen-activated protein kinase-kinase. |
| 77 | 8340422 | The c-raf-1 protooncogene encodes a Ser/Thr protein kinase. |
| 78 | 8340422 | A mitogen-activated protein kinase-kinase (MAPKK) purified from bovine brain is phosphorylated and activated 4-9-fold in vitro by c-Raf-1 from mitogen-treated cells. c-Raf-1 protein kinase activity, measured by the phosphorylation of brain MAPKK substrate, is detectably activated within 1 min after addition of platelet-derived growth factor (PDGF) to 3T3 cells, increasing more rapidly than the endogenous NIH 3T3 cell MAPKK activity. c-Raf-1 activation is also induced by insulin, phorbol ester, thrombin, and endothelin. |
| 79 | 8340422 | PDGF-, epidermal groth factor-, and insulin-stimulated 32P-c-Raf-1 yield very similar, complex tryptic 32P-peptide maps, wherein only 2 of 10 32P-peptides appear entirely de novo after growth factor addition. |
| 80 | 8340422 | Mitogen-activated protein kinase/extracellular signal-regulated kinase-2 can phosphorylate c-Raf-1 in vitro on 4-6 tryptic 32P-peptides, all of which comigrate with tryptic 32P-peptides derived from c-Raf-1 labeled in situ. |
| 81 | 8340422 | Mitogen-activated protein kinase phosphorylation of c-Raf-1 in vitro, however, does not 1) generate 32P-peptides that comigrate with those that appear de novo after PDGF or insulin treatment in situ; 2) does not convert c-Raf-1 polypeptides to a slower mobility on SDS-polyacrylamide gel electrophoresis as is seen after PDGF or insulin; 3) does not alter c-Raf-1 kinase activity toward MAPKK. |
| 82 | 8340422 | Thus, based on overlapping site specificity, Erk-2 is a viable candidate to be among the PDGF-stimulated c-Raf-1 kinases. |
| 83 | 8340422 | Although PDGF/insulin-stimulated c-Raf-1 Ser/Thr phosphorylation may be necessary to sustain the active state, a role for mitogen-activated protein kinase/extracellular signal-regulated kinase-2 phosphorylation in the initiation of c-Raf-1 activation is unlikely. |
| 84 | 8340422 | Mitogen regulation of c-Raf-1 protein kinase activity toward mitogen-activated protein kinase-kinase. |
| 85 | 8340422 | The c-raf-1 protooncogene encodes a Ser/Thr protein kinase. |
| 86 | 8340422 | A mitogen-activated protein kinase-kinase (MAPKK) purified from bovine brain is phosphorylated and activated 4-9-fold in vitro by c-Raf-1 from mitogen-treated cells. c-Raf-1 protein kinase activity, measured by the phosphorylation of brain MAPKK substrate, is detectably activated within 1 min after addition of platelet-derived growth factor (PDGF) to 3T3 cells, increasing more rapidly than the endogenous NIH 3T3 cell MAPKK activity. c-Raf-1 activation is also induced by insulin, phorbol ester, thrombin, and endothelin. |
| 87 | 8340422 | PDGF-, epidermal groth factor-, and insulin-stimulated 32P-c-Raf-1 yield very similar, complex tryptic 32P-peptide maps, wherein only 2 of 10 32P-peptides appear entirely de novo after growth factor addition. |
| 88 | 8340422 | Mitogen-activated protein kinase/extracellular signal-regulated kinase-2 can phosphorylate c-Raf-1 in vitro on 4-6 tryptic 32P-peptides, all of which comigrate with tryptic 32P-peptides derived from c-Raf-1 labeled in situ. |
| 89 | 8340422 | Mitogen-activated protein kinase phosphorylation of c-Raf-1 in vitro, however, does not 1) generate 32P-peptides that comigrate with those that appear de novo after PDGF or insulin treatment in situ; 2) does not convert c-Raf-1 polypeptides to a slower mobility on SDS-polyacrylamide gel electrophoresis as is seen after PDGF or insulin; 3) does not alter c-Raf-1 kinase activity toward MAPKK. |
| 90 | 8340422 | Thus, based on overlapping site specificity, Erk-2 is a viable candidate to be among the PDGF-stimulated c-Raf-1 kinases. |
| 91 | 8340422 | Although PDGF/insulin-stimulated c-Raf-1 Ser/Thr phosphorylation may be necessary to sustain the active state, a role for mitogen-activated protein kinase/extracellular signal-regulated kinase-2 phosphorylation in the initiation of c-Raf-1 activation is unlikely. |
| 92 | 8340422 | Mitogen regulation of c-Raf-1 protein kinase activity toward mitogen-activated protein kinase-kinase. |
| 93 | 8340422 | The c-raf-1 protooncogene encodes a Ser/Thr protein kinase. |
| 94 | 8340422 | A mitogen-activated protein kinase-kinase (MAPKK) purified from bovine brain is phosphorylated and activated 4-9-fold in vitro by c-Raf-1 from mitogen-treated cells. c-Raf-1 protein kinase activity, measured by the phosphorylation of brain MAPKK substrate, is detectably activated within 1 min after addition of platelet-derived growth factor (PDGF) to 3T3 cells, increasing more rapidly than the endogenous NIH 3T3 cell MAPKK activity. c-Raf-1 activation is also induced by insulin, phorbol ester, thrombin, and endothelin. |
| 95 | 8340422 | PDGF-, epidermal groth factor-, and insulin-stimulated 32P-c-Raf-1 yield very similar, complex tryptic 32P-peptide maps, wherein only 2 of 10 32P-peptides appear entirely de novo after growth factor addition. |
| 96 | 8340422 | Mitogen-activated protein kinase/extracellular signal-regulated kinase-2 can phosphorylate c-Raf-1 in vitro on 4-6 tryptic 32P-peptides, all of which comigrate with tryptic 32P-peptides derived from c-Raf-1 labeled in situ. |
| 97 | 8340422 | Mitogen-activated protein kinase phosphorylation of c-Raf-1 in vitro, however, does not 1) generate 32P-peptides that comigrate with those that appear de novo after PDGF or insulin treatment in situ; 2) does not convert c-Raf-1 polypeptides to a slower mobility on SDS-polyacrylamide gel electrophoresis as is seen after PDGF or insulin; 3) does not alter c-Raf-1 kinase activity toward MAPKK. |
| 98 | 8340422 | Thus, based on overlapping site specificity, Erk-2 is a viable candidate to be among the PDGF-stimulated c-Raf-1 kinases. |
| 99 | 8340422 | Although PDGF/insulin-stimulated c-Raf-1 Ser/Thr phosphorylation may be necessary to sustain the active state, a role for mitogen-activated protein kinase/extracellular signal-regulated kinase-2 phosphorylation in the initiation of c-Raf-1 activation is unlikely. |
| 100 | 8340422 | Mitogen regulation of c-Raf-1 protein kinase activity toward mitogen-activated protein kinase-kinase. |
| 101 | 8340422 | The c-raf-1 protooncogene encodes a Ser/Thr protein kinase. |
| 102 | 8340422 | A mitogen-activated protein kinase-kinase (MAPKK) purified from bovine brain is phosphorylated and activated 4-9-fold in vitro by c-Raf-1 from mitogen-treated cells. c-Raf-1 protein kinase activity, measured by the phosphorylation of brain MAPKK substrate, is detectably activated within 1 min after addition of platelet-derived growth factor (PDGF) to 3T3 cells, increasing more rapidly than the endogenous NIH 3T3 cell MAPKK activity. c-Raf-1 activation is also induced by insulin, phorbol ester, thrombin, and endothelin. |
| 103 | 8340422 | PDGF-, epidermal groth factor-, and insulin-stimulated 32P-c-Raf-1 yield very similar, complex tryptic 32P-peptide maps, wherein only 2 of 10 32P-peptides appear entirely de novo after growth factor addition. |
| 104 | 8340422 | Mitogen-activated protein kinase/extracellular signal-regulated kinase-2 can phosphorylate c-Raf-1 in vitro on 4-6 tryptic 32P-peptides, all of which comigrate with tryptic 32P-peptides derived from c-Raf-1 labeled in situ. |
| 105 | 8340422 | Mitogen-activated protein kinase phosphorylation of c-Raf-1 in vitro, however, does not 1) generate 32P-peptides that comigrate with those that appear de novo after PDGF or insulin treatment in situ; 2) does not convert c-Raf-1 polypeptides to a slower mobility on SDS-polyacrylamide gel electrophoresis as is seen after PDGF or insulin; 3) does not alter c-Raf-1 kinase activity toward MAPKK. |
| 106 | 8340422 | Thus, based on overlapping site specificity, Erk-2 is a viable candidate to be among the PDGF-stimulated c-Raf-1 kinases. |
| 107 | 8340422 | Although PDGF/insulin-stimulated c-Raf-1 Ser/Thr phosphorylation may be necessary to sustain the active state, a role for mitogen-activated protein kinase/extracellular signal-regulated kinase-2 phosphorylation in the initiation of c-Raf-1 activation is unlikely. |
| 108 | 8340422 | Mitogen regulation of c-Raf-1 protein kinase activity toward mitogen-activated protein kinase-kinase. |
| 109 | 8340422 | The c-raf-1 protooncogene encodes a Ser/Thr protein kinase. |
| 110 | 8340422 | A mitogen-activated protein kinase-kinase (MAPKK) purified from bovine brain is phosphorylated and activated 4-9-fold in vitro by c-Raf-1 from mitogen-treated cells. c-Raf-1 protein kinase activity, measured by the phosphorylation of brain MAPKK substrate, is detectably activated within 1 min after addition of platelet-derived growth factor (PDGF) to 3T3 cells, increasing more rapidly than the endogenous NIH 3T3 cell MAPKK activity. c-Raf-1 activation is also induced by insulin, phorbol ester, thrombin, and endothelin. |
| 111 | 8340422 | PDGF-, epidermal groth factor-, and insulin-stimulated 32P-c-Raf-1 yield very similar, complex tryptic 32P-peptide maps, wherein only 2 of 10 32P-peptides appear entirely de novo after growth factor addition. |
| 112 | 8340422 | Mitogen-activated protein kinase/extracellular signal-regulated kinase-2 can phosphorylate c-Raf-1 in vitro on 4-6 tryptic 32P-peptides, all of which comigrate with tryptic 32P-peptides derived from c-Raf-1 labeled in situ. |
| 113 | 8340422 | Mitogen-activated protein kinase phosphorylation of c-Raf-1 in vitro, however, does not 1) generate 32P-peptides that comigrate with those that appear de novo after PDGF or insulin treatment in situ; 2) does not convert c-Raf-1 polypeptides to a slower mobility on SDS-polyacrylamide gel electrophoresis as is seen after PDGF or insulin; 3) does not alter c-Raf-1 kinase activity toward MAPKK. |
| 114 | 8340422 | Thus, based on overlapping site specificity, Erk-2 is a viable candidate to be among the PDGF-stimulated c-Raf-1 kinases. |
| 115 | 8340422 | Although PDGF/insulin-stimulated c-Raf-1 Ser/Thr phosphorylation may be necessary to sustain the active state, a role for mitogen-activated protein kinase/extracellular signal-regulated kinase-2 phosphorylation in the initiation of c-Raf-1 activation is unlikely. |
| 116 | 8665940 | Effect of tumor necrosis factor-alpha on insulin-stimulated mitogen-activated protein kinase cascade in cultured rat skeletal muscle cells. |
| 117 | 8665940 | Tumor necrosis factor-alpha (TNF-alpha) is a proposed mediator of insulin resistance in obese/diabetic animals through its effects on tyrosine phosphorylation of the insulin receptor and its substrate, insulin receptor substrate-1. |
| 118 | 8665940 | In this study, the acute effects of TNF-alpha on the mitogen-activated protein kinase (MAPK) signalling cascade were examined in cultured rat skeletal muscle cell line, L6. |
| 119 | 8665940 | Insulin treatment of L6 cells resulted in a rapid increase in MAPK activity (> twofold in 5 min with 10 nM insulin). |
| 120 | 8665940 | Prior treatment with TNF-alpha for 60 min blocked subsequent insulin-induced activation of MAPK in a dose- and time-dependent manner. |
| 121 | 8665940 | Metabolic labelling studies with inorganic [32P]phosphate followed by immuno-precipitation of MAPK and its upstream activator, mitogen-activated protein kinase kinase, indicated decreased phosphorylation of MAPK and its kinase in response to insulin in cells exposed to TNF-alpha. |
| 122 | 8665940 | This effect of TNF-alpha was not due to inhibition of insulin-stimulated p21ras-GTP loading or Raf-1 phosphorylation. |
| 123 | 8665940 | Low concentrations (2 nM) of okadaic acid, a serine/threonine phosphatase inhibitor, prevented TNF-alpha-induced inhibition of MAPK and restored insulin's effect on MAPK activity, while orthovanadate (a tyrosine phosphatase inhibitor), inhibitor 2 (phosphatase-1 inhibitor) and FK506 (phosphatase-2B inhibitor) were ineffective. |
| 124 | 8665940 | These results suggested an involvement of an okadaic-acid-sensitive serine/threonine phosphatase in TNF-alpha-induced blockade of insulin's effect on MAPK and/or its kinase. |
| 125 | 8665940 | Therefore, we examined the effect of TNF-alpha on protein phosphatase-1 (PP-1) and protein phosphatase-2A (PP-2A) activities. |
| 126 | 8665940 | As reported by us earlier, insulin rapidly stimulated PP-1 and concomitantly inhibited PP-2A activities in control cells. |
| 127 | 8665940 | TNF-alpha treatment blocked insulin-induced activation of PP-1. |
| 128 | 8665940 | In contrast to PP-1, TNF-alpha caused a 60% increase in PP-2A activity and insulin failed to prevent this TNF-alpha effect. |
| 129 | 8665940 | The time course of PP-2A activation by TNF-alpha preceded the kinetics of inhibition of MAPK. |
| 130 | 8665940 | Cell-permeable ceramide analogs mimicked the TNF-alpha effect on MAPK inhibition and PP-2A activation. |
| 131 | 8665940 | We conclude that TNF-alpha abrogates the insulin effect on MAPK activation by increasing dephosphorylation of MAPK kinase via an activated phosphatase. |
| 132 | 8964184 | In order to elucidate the signal transduction pathway from external mechanical stress to nuclear gene expression in mechanical stress-induced cardiac hypertrophy, we examined the time course of activation of Raf-1 kinase (Raf-1), mitogen-activated protein kinase kinase (MAPKK) and MAP kinases (MAPKs) in neonatal rat cardiac myocytes. |
| 133 | 8964184 | When the stretch-conditioned culture medium was transferred to non-stretched cardiac myocytes, the medium activated MAPK activity slightly but significantly, and the activation was completely blocked by the type I angiotensin II (AngII) receptor antagonist, CV-11974. |
| 134 | 8964184 | These results suggest that mechanical stress activates the protein kinase cascade of phosphorylation in cardiac myocytes in the order of Raf-1, MAPKK and MAPKs. |
| 135 | 8964184 | In order to elucidate the signal transduction pathway from external mechanical stress to nuclear gene expression in mechanical stress-induced cardiac hypertrophy, we examined the time course of activation of Raf-1 kinase (Raf-1), mitogen-activated protein kinase kinase (MAPKK) and MAP kinases (MAPKs) in neonatal rat cardiac myocytes. |
| 136 | 8964184 | When the stretch-conditioned culture medium was transferred to non-stretched cardiac myocytes, the medium activated MAPK activity slightly but significantly, and the activation was completely blocked by the type I angiotensin II (AngII) receptor antagonist, CV-11974. |
| 137 | 8964184 | These results suggest that mechanical stress activates the protein kinase cascade of phosphorylation in cardiac myocytes in the order of Raf-1, MAPKK and MAPKs. |
| 138 | 8972184 | Mutation of Raf Cys 165 and Cys 168 to Ser strongly inhibits the Ras-dependent activation of c-Raf-1 by epidermal growth factor (EGF). |
| 139 | 8972184 | Deletion of the Raf zinc finger and replacement with a homologous zinc finger from protein kinase C gamma (PKC gamma) (to give gamma/Raf) also abrogates EGF-induced activation but enables a vigorous phorbol myristate acetate (PMA)-induced activation. |
| 140 | 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. |
| 141 | 9133538 | Mitogen-activated protein (MAP) kinase plays crucial roles in cell growth and differentiation. |
| 142 | 9133538 | It has recently been shown that the MAP kinase cascade in growth factor signaling diverges and cross-talks with other signaling pathways. |
| 143 | 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). |
| 144 | 9133538 | The effect of LY294002, a structurally distinct PI3-kinase inhibitor, on the activation of Raf-1 kinase by both ligands was also examined. |
| 145 | 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. |
| 146 | 9133538 | One hundred micromol/l LY294002 blocked insulin-induced activation of Raf-1 kinase without affecting EGF-induced activation of this kinase. |
| 147 | 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. |
| 148 | 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. |
| 149 | 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. |
| 150 | 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. |
| 151 | 9133538 | Mitogen-activated protein (MAP) kinase plays crucial roles in cell growth and differentiation. |
| 152 | 9133538 | It has recently been shown that the MAP kinase cascade in growth factor signaling diverges and cross-talks with other signaling pathways. |
| 153 | 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). |
| 154 | 9133538 | The effect of LY294002, a structurally distinct PI3-kinase inhibitor, on the activation of Raf-1 kinase by both ligands was also examined. |
| 155 | 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. |
| 156 | 9133538 | One hundred micromol/l LY294002 blocked insulin-induced activation of Raf-1 kinase without affecting EGF-induced activation of this kinase. |
| 157 | 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. |
| 158 | 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. |
| 159 | 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. |
| 160 | 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. |
| 161 | 9133538 | Mitogen-activated protein (MAP) kinase plays crucial roles in cell growth and differentiation. |
| 162 | 9133538 | It has recently been shown that the MAP kinase cascade in growth factor signaling diverges and cross-talks with other signaling pathways. |
| 163 | 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). |
| 164 | 9133538 | The effect of LY294002, a structurally distinct PI3-kinase inhibitor, on the activation of Raf-1 kinase by both ligands was also examined. |
| 165 | 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. |
| 166 | 9133538 | One hundred micromol/l LY294002 blocked insulin-induced activation of Raf-1 kinase without affecting EGF-induced activation of this kinase. |
| 167 | 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. |
| 168 | 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. |
| 169 | 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. |
| 170 | 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. |
| 171 | 9133538 | Mitogen-activated protein (MAP) kinase plays crucial roles in cell growth and differentiation. |
| 172 | 9133538 | It has recently been shown that the MAP kinase cascade in growth factor signaling diverges and cross-talks with other signaling pathways. |
| 173 | 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). |
| 174 | 9133538 | The effect of LY294002, a structurally distinct PI3-kinase inhibitor, on the activation of Raf-1 kinase by both ligands was also examined. |
| 175 | 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. |
| 176 | 9133538 | One hundred micromol/l LY294002 blocked insulin-induced activation of Raf-1 kinase without affecting EGF-induced activation of this kinase. |
| 177 | 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. |
| 178 | 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. |
| 179 | 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. |
| 180 | 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. |
| 181 | 9133538 | Mitogen-activated protein (MAP) kinase plays crucial roles in cell growth and differentiation. |
| 182 | 9133538 | It has recently been shown that the MAP kinase cascade in growth factor signaling diverges and cross-talks with other signaling pathways. |
| 183 | 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). |
| 184 | 9133538 | The effect of LY294002, a structurally distinct PI3-kinase inhibitor, on the activation of Raf-1 kinase by both ligands was also examined. |
| 185 | 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. |
| 186 | 9133538 | One hundred micromol/l LY294002 blocked insulin-induced activation of Raf-1 kinase without affecting EGF-induced activation of this kinase. |
| 187 | 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. |
| 188 | 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. |
| 189 | 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. |
| 190 | 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. |
| 191 | 9133538 | Mitogen-activated protein (MAP) kinase plays crucial roles in cell growth and differentiation. |
| 192 | 9133538 | It has recently been shown that the MAP kinase cascade in growth factor signaling diverges and cross-talks with other signaling pathways. |
| 193 | 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). |
| 194 | 9133538 | The effect of LY294002, a structurally distinct PI3-kinase inhibitor, on the activation of Raf-1 kinase by both ligands was also examined. |
| 195 | 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. |
| 196 | 9133538 | One hundred micromol/l LY294002 blocked insulin-induced activation of Raf-1 kinase without affecting EGF-induced activation of this kinase. |
| 197 | 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. |
| 198 | 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. |
| 199 | 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. |
| 200 | 9165048 | Mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways are not sufficient for insulin-like growth factor I-induced mitogenesis and tumorigenesis. |
| 201 | 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). |
| 202 | 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. |
| 203 | 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. |
| 204 | 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. |
| 205 | 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. |
| 206 | 9175762 | The proto-oncogene Crk-II enhances apoptosis by a Ras-dependent, Raf-1/MAP kinase-independent pathway. |
| 207 | 9175762 | The results presented here suggest that overexpression of Crk-II induces apoptosis via a Ras-dependent, Raf-1/MEK1/ERK-independent pathway. |
| 208 | 9175762 | The proto-oncogene Crk-II enhances apoptosis by a Ras-dependent, Raf-1/MAP kinase-independent pathway. |
| 209 | 9175762 | The results presented here suggest that overexpression of Crk-II induces apoptosis via a Ras-dependent, Raf-1/MEK1/ERK-independent pathway. |
| 210 | 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. |
| 211 | 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. |
| 212 | 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. |
| 213 | 9688610 | Raf-1 kinase and MAP kinase kinase, upstream activators of ERK, were also markedly stimulated in all subjects. |
| 214 | 9688610 | In addition, c-Jun NH2-terminal kinase and p38 kinase, components of two parallel MAP kinase pathways, were activated following muscle injury. |
| 215 | 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. |
| 216 | 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. |
| 217 | 10329981 | Differential regulation of MAP kinase, p70(S6K), and Akt by contraction and insulin in rat skeletal muscle. |
| 218 | 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. |
| 219 | 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. |
| 220 | 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. |
| 221 | 10329981 | Insulin was considerably less effective than contraction in stimulating the MAP kinase pathway. |
| 222 | 10329981 | However, insulin, but not contraction, increased p70(S6K) and Akt activities in the muscle. |
| 223 | 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. |
| 224 | 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. |
| 225 | 10329981 | Differential regulation of MAP kinase, p70(S6K), and Akt by contraction and insulin in rat skeletal muscle. |
| 226 | 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. |
| 227 | 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. |
| 228 | 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. |
| 229 | 10329981 | Insulin was considerably less effective than contraction in stimulating the MAP kinase pathway. |
| 230 | 10329981 | However, insulin, but not contraction, increased p70(S6K) and Akt activities in the muscle. |
| 231 | 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. |
| 232 | 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. |
| 233 | 11027130 | Cell treatment with manumycin blocked insulin's ability to suppress pro-apoptotic caspase-3 activity which led to time-dependent proteolytic cleavage of two nuclear target proteins. |
| 234 | 11027130 | The Raf-1/MEK/ERK cascade and the serine/threonine protein kinase Akt are two survival pathways that may be activated in response to insulin. |
| 235 | 11027130 | We tested the hypothesis that inhibition of farnesylated Ras was causally related to manumycin-induced apoptosis and showed that the response to manumycin was found to be independent of K-Ras function because membrane association and activation of endogenous K-Ras proteins in terms of GTP loading and ERK activation were unabated following treatment with manumycin. |
| 236 | 11027130 | Moreover, blocking p21Ras/Raf-1/MEK/ERK cascade by the expression of a transdominant inhibitory mSOS1 mutant in CHO-IR cells kept cells sensitive to the antiapoptotic action of insulin. |
| 237 | 11027130 | Insulin-dependent activation of Akt was blocked by 4 h treatment with manumycin (P < 0.01), a kinetic too rapid to be explained by Ras inhibition. |
| 238 | 11027130 | This study suggests that the depletion of short-lived farnesylated proteins by manumycin suppresses the antiapoptotic action of insulin at least in part by disrupting Akt activation but not that of the K-Ras/Raf-1/ERK-dependent cascade. |
| 239 | 11027130 | Cell treatment with manumycin blocked insulin's ability to suppress pro-apoptotic caspase-3 activity which led to time-dependent proteolytic cleavage of two nuclear target proteins. |
| 240 | 11027130 | The Raf-1/MEK/ERK cascade and the serine/threonine protein kinase Akt are two survival pathways that may be activated in response to insulin. |
| 241 | 11027130 | We tested the hypothesis that inhibition of farnesylated Ras was causally related to manumycin-induced apoptosis and showed that the response to manumycin was found to be independent of K-Ras function because membrane association and activation of endogenous K-Ras proteins in terms of GTP loading and ERK activation were unabated following treatment with manumycin. |
| 242 | 11027130 | Moreover, blocking p21Ras/Raf-1/MEK/ERK cascade by the expression of a transdominant inhibitory mSOS1 mutant in CHO-IR cells kept cells sensitive to the antiapoptotic action of insulin. |
| 243 | 11027130 | Insulin-dependent activation of Akt was blocked by 4 h treatment with manumycin (P < 0.01), a kinetic too rapid to be explained by Ras inhibition. |
| 244 | 11027130 | This study suggests that the depletion of short-lived farnesylated proteins by manumycin suppresses the antiapoptotic action of insulin at least in part by disrupting Akt activation but not that of the K-Ras/Raf-1/ERK-dependent cascade. |
| 245 | 11027130 | Cell treatment with manumycin blocked insulin's ability to suppress pro-apoptotic caspase-3 activity which led to time-dependent proteolytic cleavage of two nuclear target proteins. |
| 246 | 11027130 | The Raf-1/MEK/ERK cascade and the serine/threonine protein kinase Akt are two survival pathways that may be activated in response to insulin. |
| 247 | 11027130 | We tested the hypothesis that inhibition of farnesylated Ras was causally related to manumycin-induced apoptosis and showed that the response to manumycin was found to be independent of K-Ras function because membrane association and activation of endogenous K-Ras proteins in terms of GTP loading and ERK activation were unabated following treatment with manumycin. |
| 248 | 11027130 | Moreover, blocking p21Ras/Raf-1/MEK/ERK cascade by the expression of a transdominant inhibitory mSOS1 mutant in CHO-IR cells kept cells sensitive to the antiapoptotic action of insulin. |
| 249 | 11027130 | Insulin-dependent activation of Akt was blocked by 4 h treatment with manumycin (P < 0.01), a kinetic too rapid to be explained by Ras inhibition. |
| 250 | 11027130 | This study suggests that the depletion of short-lived farnesylated proteins by manumycin suppresses the antiapoptotic action of insulin at least in part by disrupting Akt activation but not that of the K-Ras/Raf-1/ERK-dependent cascade. |
| 251 | 11274179 | Incubation of cells with nocodazole leads to activation of Pak1/2, kinases downstream of small GTPases Rac/Cdc42, which have been previously indicated to phosphorylate Raf-1 Ser(338). |
| 252 | 11274179 | Nocodazole-induced stimulation of Raf-1 is augmented by co-expression of small GTPases Rac/Cdc42 and Pak1/2. |
| 253 | 11274179 | Dominant negative mutants of these proteins block activation of Raf-1 by nocodazole, but not by epidermal growth factor (EGF). |
| 254 | 11274179 | Thus, our studies define Rac/Cdc42/Pak as a module upstream of Raf-1 during its activation by microtubule disruption. |
| 255 | 11274179 | Finally, an in vitro kinase assay demonstrates that the zinc finger mutant serves as a better substrate of Pak1 than the wild type Raf-1. |
| 256 | 11274179 | Collectively, our results indicate that 1) the zinc finger exerts an inhibitory effect on Raf-1 activation, probably by preventing phosphorylation of (338)SSYY(341); 2) such inhibition is first overcome by an unknown factor binding in place of Ras-GTP to the amino-terminal regulatory region in response to nocodazole; and 3) EGF and nocodazole utilize different kinases to phosphorylate Ser(338), an event crucial for Raf activation. |
| 257 | 11274179 | Incubation of cells with nocodazole leads to activation of Pak1/2, kinases downstream of small GTPases Rac/Cdc42, which have been previously indicated to phosphorylate Raf-1 Ser(338). |
| 258 | 11274179 | Nocodazole-induced stimulation of Raf-1 is augmented by co-expression of small GTPases Rac/Cdc42 and Pak1/2. |
| 259 | 11274179 | Dominant negative mutants of these proteins block activation of Raf-1 by nocodazole, but not by epidermal growth factor (EGF). |
| 260 | 11274179 | Thus, our studies define Rac/Cdc42/Pak as a module upstream of Raf-1 during its activation by microtubule disruption. |
| 261 | 11274179 | Finally, an in vitro kinase assay demonstrates that the zinc finger mutant serves as a better substrate of Pak1 than the wild type Raf-1. |
| 262 | 11274179 | Collectively, our results indicate that 1) the zinc finger exerts an inhibitory effect on Raf-1 activation, probably by preventing phosphorylation of (338)SSYY(341); 2) such inhibition is first overcome by an unknown factor binding in place of Ras-GTP to the amino-terminal regulatory region in response to nocodazole; and 3) EGF and nocodazole utilize different kinases to phosphorylate Ser(338), an event crucial for Raf activation. |
| 263 | 11274179 | Incubation of cells with nocodazole leads to activation of Pak1/2, kinases downstream of small GTPases Rac/Cdc42, which have been previously indicated to phosphorylate Raf-1 Ser(338). |
| 264 | 11274179 | Nocodazole-induced stimulation of Raf-1 is augmented by co-expression of small GTPases Rac/Cdc42 and Pak1/2. |
| 265 | 11274179 | Dominant negative mutants of these proteins block activation of Raf-1 by nocodazole, but not by epidermal growth factor (EGF). |
| 266 | 11274179 | Thus, our studies define Rac/Cdc42/Pak as a module upstream of Raf-1 during its activation by microtubule disruption. |
| 267 | 11274179 | Finally, an in vitro kinase assay demonstrates that the zinc finger mutant serves as a better substrate of Pak1 than the wild type Raf-1. |
| 268 | 11274179 | Collectively, our results indicate that 1) the zinc finger exerts an inhibitory effect on Raf-1 activation, probably by preventing phosphorylation of (338)SSYY(341); 2) such inhibition is first overcome by an unknown factor binding in place of Ras-GTP to the amino-terminal regulatory region in response to nocodazole; and 3) EGF and nocodazole utilize different kinases to phosphorylate Ser(338), an event crucial for Raf activation. |
| 269 | 11274179 | Incubation of cells with nocodazole leads to activation of Pak1/2, kinases downstream of small GTPases Rac/Cdc42, which have been previously indicated to phosphorylate Raf-1 Ser(338). |
| 270 | 11274179 | Nocodazole-induced stimulation of Raf-1 is augmented by co-expression of small GTPases Rac/Cdc42 and Pak1/2. |
| 271 | 11274179 | Dominant negative mutants of these proteins block activation of Raf-1 by nocodazole, but not by epidermal growth factor (EGF). |
| 272 | 11274179 | Thus, our studies define Rac/Cdc42/Pak as a module upstream of Raf-1 during its activation by microtubule disruption. |
| 273 | 11274179 | Finally, an in vitro kinase assay demonstrates that the zinc finger mutant serves as a better substrate of Pak1 than the wild type Raf-1. |
| 274 | 11274179 | Collectively, our results indicate that 1) the zinc finger exerts an inhibitory effect on Raf-1 activation, probably by preventing phosphorylation of (338)SSYY(341); 2) such inhibition is first overcome by an unknown factor binding in place of Ras-GTP to the amino-terminal regulatory region in response to nocodazole; and 3) EGF and nocodazole utilize different kinases to phosphorylate Ser(338), an event crucial for Raf activation. |
| 275 | 11274179 | Incubation of cells with nocodazole leads to activation of Pak1/2, kinases downstream of small GTPases Rac/Cdc42, which have been previously indicated to phosphorylate Raf-1 Ser(338). |
| 276 | 11274179 | Nocodazole-induced stimulation of Raf-1 is augmented by co-expression of small GTPases Rac/Cdc42 and Pak1/2. |
| 277 | 11274179 | Dominant negative mutants of these proteins block activation of Raf-1 by nocodazole, but not by epidermal growth factor (EGF). |
| 278 | 11274179 | Thus, our studies define Rac/Cdc42/Pak as a module upstream of Raf-1 during its activation by microtubule disruption. |
| 279 | 11274179 | Finally, an in vitro kinase assay demonstrates that the zinc finger mutant serves as a better substrate of Pak1 than the wild type Raf-1. |
| 280 | 11274179 | Collectively, our results indicate that 1) the zinc finger exerts an inhibitory effect on Raf-1 activation, probably by preventing phosphorylation of (338)SSYY(341); 2) such inhibition is first overcome by an unknown factor binding in place of Ras-GTP to the amino-terminal regulatory region in response to nocodazole; and 3) EGF and nocodazole utilize different kinases to phosphorylate Ser(338), an event crucial for Raf activation. |
| 281 | 11274179 | Incubation of cells with nocodazole leads to activation of Pak1/2, kinases downstream of small GTPases Rac/Cdc42, which have been previously indicated to phosphorylate Raf-1 Ser(338). |
| 282 | 11274179 | Nocodazole-induced stimulation of Raf-1 is augmented by co-expression of small GTPases Rac/Cdc42 and Pak1/2. |
| 283 | 11274179 | Dominant negative mutants of these proteins block activation of Raf-1 by nocodazole, but not by epidermal growth factor (EGF). |
| 284 | 11274179 | Thus, our studies define Rac/Cdc42/Pak as a module upstream of Raf-1 during its activation by microtubule disruption. |
| 285 | 11274179 | Finally, an in vitro kinase assay demonstrates that the zinc finger mutant serves as a better substrate of Pak1 than the wild type Raf-1. |
| 286 | 11274179 | Collectively, our results indicate that 1) the zinc finger exerts an inhibitory effect on Raf-1 activation, probably by preventing phosphorylation of (338)SSYY(341); 2) such inhibition is first overcome by an unknown factor binding in place of Ras-GTP to the amino-terminal regulatory region in response to nocodazole; and 3) EGF and nocodazole utilize different kinases to phosphorylate Ser(338), an event crucial for Raf activation. |
| 287 | 11733498 | Interaction between active Pak1 and Raf-1 is necessary for phosphorylation and activation of Raf-1. |
| 288 | 11733498 | Previous studies have shown that Pak1/2 is implicated in both Ras-dependent and -independent activation of Raf-1 by phosphorylating Raf Ser(338). |
| 289 | 11733498 | The present study explores the structural basis of Raf-1 phosphorylation by Pak1. |
| 290 | 11733498 | Interaction between active Pak1 and Raf-1 is necessary for phosphorylation and activation of Raf-1. |
| 291 | 11733498 | Previous studies have shown that Pak1/2 is implicated in both Ras-dependent and -independent activation of Raf-1 by phosphorylating Raf Ser(338). |
| 292 | 11733498 | The present study explores the structural basis of Raf-1 phosphorylation by Pak1. |
| 293 | 11733498 | Interaction between active Pak1 and Raf-1 is necessary for phosphorylation and activation of Raf-1. |
| 294 | 11733498 | Previous studies have shown that Pak1/2 is implicated in both Ras-dependent and -independent activation of Raf-1 by phosphorylating Raf Ser(338). |
| 295 | 11733498 | The present study explores the structural basis of Raf-1 phosphorylation by Pak1. |
| 296 | 11937295 | Promoter assay showed that the induction of VEGF was dependent on AP-1. |
| 297 | 11937295 | The activity of Ras/Raf-1/MEK/ERK1/2 was involved in the CML-BSA-stimulated signaling pathways to activate the AP-1 transcription with a peak at 1 h. |
| 298 | 11937295 | AGE-BSA also induced VEGF mediated by AP-1, however, there was a difference of effect between AGE-BSA and CML-BSA in the activation of AP-1. |
| 299 | 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. |
| 300 | 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). |
| 301 | 11991199 | Initiation of DNA synthesis was preceded by activation of Raf-1, MEK and MAP kinases (Erk 1 and Erk2). |
| 302 | 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. |
| 303 | 11991199 | PDGF also stimulated phosphorylation of protein kinase B (Akt/PKB) and p70 S6Kinase (p70S6K) in a wortmannin-sensitive manner. |
| 304 | 11991199 | Low concentrations of insulin (1-10 nmol/l) alone showed little mitogenic activity and no significant effect on MAPK activity. |
| 305 | 11991199 | However, the presence of insulin enhanced both DNA synthesis and MAPK activation by PDGF. |
| 306 | 11991199 | Insulin was without effect on PDGF-stimulated activations of protein kinase B (Akt/PKB) and p70S6K. |
| 307 | 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. |
| 308 | 12006386 | The overexpression of dominant-negative p47phox in A10 cells suppressed lysoPC-induced ERK activation. |
| 309 | 12006386 | The ROS-dependent ERK activation by lysoPC seems to involve protein kinase C- and Ras-dependent raf-1 activation. |
| 310 | 12006386 | Induction of c-fos expression and enhanced AP-1 binding activity by lysoPC were also inhibited by DPI and NAC. |
| 311 | 12006386 | Taken together, these data suggest that ROS generated by NADH/NADPH oxidase contribute to lysoPC-induced activation of ERK1/2 and subsequent growth promotion in VSMCs. |
| 312 | 12147223 | Here, we show that adducts of N(epsilon)-(carboxymethyl)lysine (CML), a major AGE, and bovine serum albumin (CML-BSA) stimulated gamma-glutamylcysteine synthetase (gamma-GCS), which is a key enzyme of glutathione (GSH) synthesis, in RAW264.7 mouse macrophage-like cells. |
| 313 | 12147223 | CML-BSA also stimulated DNA-binding activity of activator protein-1 (AP-1) within 3h, but the stimulatory effect decreased in 5h, and nuclear factor-kappaB (NF-kappaB) with a peak activity at 1h and the stimulatory effect diminished in 3h. |
| 314 | 12147223 | CML-BSA also stimulated the activity of protein kinase C, Ras/Raf-1, and MEK/ERK1/2. |
| 315 | 12147223 | Inhibition of ERK1/2 abolished CML-BSA-stimulated AP-1 DNA-binding activity and gamma-GCSh mRNA expression. |
| 316 | 12196513 | High glucose stimulates synthesis of fibronectin via a novel protein kinase C, Rap1b, and B-Raf signaling pathway. |
| 317 | 12196513 | This investigation describes the effect of high glucose (HG) on a small GTP-binding protein, Rap1b, expression and activation, and the relevance of protein kinase C (PKC) and Raf pathways in fibronectin synthesis in cultured renal glomerular mesangial cells (MCs). |
| 318 | 12196513 | B-Raf and Raf-1 expression was investigated to assess whether Rap1b effects are mediated via the Raf pathway. |
| 319 | 12196513 | B-Raf, and not Raf-1, expression was increased in MCs transfected with Rap1b. |
| 320 | 12196513 | HG also caused activation of Rap1b, which was largely unaffected by anti-platelet-derived growth factor (PDGF) antibodies. |
| 321 | 12196513 | HG-induced activation of Rap1b was specific, since Rap2b activation and expression of Rap2a and Rap2b were unaffected by HG. |
| 322 | 12196513 | This effect appears to be PKC-dependent and PDGF-independent, but involves B-Raf, suggesting a novel PKC-Rap1b-B-Raf pathway responsible for HG-induced increased mesangial matrix synthesis, a hallmark of diabetic nephropathy. |
| 323 | 12196513 | High glucose stimulates synthesis of fibronectin via a novel protein kinase C, Rap1b, and B-Raf signaling pathway. |
| 324 | 12196513 | This investigation describes the effect of high glucose (HG) on a small GTP-binding protein, Rap1b, expression and activation, and the relevance of protein kinase C (PKC) and Raf pathways in fibronectin synthesis in cultured renal glomerular mesangial cells (MCs). |
| 325 | 12196513 | B-Raf and Raf-1 expression was investigated to assess whether Rap1b effects are mediated via the Raf pathway. |
| 326 | 12196513 | B-Raf, and not Raf-1, expression was increased in MCs transfected with Rap1b. |
| 327 | 12196513 | HG also caused activation of Rap1b, which was largely unaffected by anti-platelet-derived growth factor (PDGF) antibodies. |
| 328 | 12196513 | HG-induced activation of Rap1b was specific, since Rap2b activation and expression of Rap2a and Rap2b were unaffected by HG. |
| 329 | 12196513 | This effect appears to be PKC-dependent and PDGF-independent, but involves B-Raf, suggesting a novel PKC-Rap1b-B-Raf pathway responsible for HG-induced increased mesangial matrix synthesis, a hallmark of diabetic nephropathy. |
| 330 | 12244094 | Phosphorylation of 338SSYY341 regulates specific interaction between Raf-1 and MEK1. |
| 331 | 12244094 | The present study characterizes the interaction between the Raf-1 kinase domain and MEK1 and examines whether the magnitude of their interaction correlates to the ability of Raf to phosphorylate MEK1. |
| 332 | 12244094 | We also show that the integrity of the Raf ATP-binding site is necessary for the interaction between Raf-1 and MEK1. |
| 333 | 12244094 | Phosphorylation of 338SSYY341 regulates specific interaction between Raf-1 and MEK1. |
| 334 | 12244094 | The present study characterizes the interaction between the Raf-1 kinase domain and MEK1 and examines whether the magnitude of their interaction correlates to the ability of Raf to phosphorylate MEK1. |
| 335 | 12244094 | We also show that the integrity of the Raf ATP-binding site is necessary for the interaction between Raf-1 and MEK1. |
| 336 | 12244094 | Phosphorylation of 338SSYY341 regulates specific interaction between Raf-1 and MEK1. |
| 337 | 12244094 | The present study characterizes the interaction between the Raf-1 kinase domain and MEK1 and examines whether the magnitude of their interaction correlates to the ability of Raf to phosphorylate MEK1. |
| 338 | 12244094 | We also show that the integrity of the Raf ATP-binding site is necessary for the interaction between Raf-1 and MEK1. |
| 339 | 12647305 | Involvement of MEKK1/ERK/P21Waf1/Cip1 signal transduction pathway in inhibition of IGF-I-mediated cell growth response by methylglyoxal. |
| 340 | 12647305 | These disturbances could modify the cell response to hormones and growth factors, including insulin-like growth factor-1 (IGF-I). |
| 341 | 12647305 | MG rendered these cells resistant to the mitogenic action of IGF-I, and this was associated with stronger and prolonged activation of ERK and over-expression of P21(Waf1/Cip1). |
| 342 | 12647305 | The synergistic effect of MG with IGF-I in activation of ERK was completely abolished by PD98059 but not by a specific PI3K inhibitor, LY294002, or a specific PKC inhibitor, bisindolylmaleimide. |
| 343 | 12647305 | Blocking of Raf-1 activity by expression of a dominant negative form of Raf-1 did not reduce the enhancing effect of MG on IGF-I-induced activation of ERK. |
| 344 | 12647305 | However, transfection of a catalytically inactive form of MEKK1 resulted in inactivation of the MG-induced activation of ERK and partial inhibition of the enhanced activation of ERK and over-expression of p21(Waf1/Cip1) induced by co-stimulation of MG and IGF-I. |
| 345 | 12647305 | These results suggested that the alteration of intracellular milieu induced by MG through a MEKK1-mediated and PI3K/PKC/Raf-1-independent pathway resulted in the modification of cell response to IGF-I for p21(Waf1/Cip1)-mediated growth arrest, which may be one of the crucial mechanisms for MG to promote the development of chronic clinical complications in diabetes. |
| 346 | 12663469 | Differential activation mechanisms of Erk-1/2 and p70(S6K) by glucose in pancreatic beta-cells. |
| 347 | 12663469 | Glucose can activate the mitogen-activated kinases, Erk-1/2, and the ribosomal-S6 kinase, p70(S6K), in beta-cells, contributing to an increase in mitogenesis. |
| 348 | 12663469 | However, the signaling mechanism by which glucose induces Erk-1/2 and p70(S6K) phosphorylation activation is undefined. |
| 349 | 12663469 | Increased glucose metabolism increases [Ca(2+)](i) and [cAMP], and it was investigated if these secondary signals were linked to glucose-induced Erk-1/2 and p70(S6K) activation in pancreatic beta-cells. |
| 350 | 12663469 | Blocking Ca(2+) influx with verapamil, or inhibiting protein kinase A (PKA) with H89, prevented glucose-induced Erk-1/2 phosphorylation. |
| 351 | 12663469 | Collectively, our study indicates that a glucose-induced rise in [Ca(2+)](i) leads to cAMP-induced activation of PKA that acts downstream of Ras and upstream of the MAP/Erk kinase, MEK, to mediate Erk-1/2 phosphorylation via phosphorylation activation of Raf-1. |
| 352 | 12663469 | In contrast, glucose-induced p70(S6K) activation, in the same beta-cells, was mediated by a distinct signaling pathway independent of Ca(2+)/cAMP, most likely via mTOR-kinase acting as an "ATP-sensor." |
| 353 | 12688637 | Also, we report immunologic localization of H-Ras regulatory proteins including its nucleotide exchange factor (GRF-1) and its effector protein (eg., Raf-1) in isolated beta-cells. |
| 354 | 12956399 | Also content of phoshorylated c-Raf kinase (an upstream activator of ERKs) was slightly increased at baseline conditions in the diabetic samples. |
| 355 | 15093669 | While vanadium deficiency accounts for several physiological malfunctionings including thyroid, glucose and lipid metabolism, etc., several genes are regulated by this element or by its compounds, which include genes for tumor necrosis factor-alpha (TNF-alpha), Interleukin-8 (IL-8), activator protein-1 (AP-1), ras, c-raf-1, mitogen activated protein kinase (MAPK), p53, nuclear factors-kappaB, etc. |
| 356 | 15520221 | Insulin receptor, insulin receptor substrate-1, Raf-1, and Mek-1 during hormonal hepatocarcinogenesis by intrahepatic pancreatic islet transplantation in diabetic rats. |
| 357 | 15520221 | Thus, we investigated FAHs, HCAs, and HCCs for altered expression of insulin receptor, insulin receptor substrate-1 (IRS-1), Raf-1 and Mek-1. |
| 358 | 15520221 | IRS-1, Raf-1, and Mek-1 proteins were strongly overexpressed in FAHs and tumors, as compared with the unaltered liver tissue. |
| 359 | 15520221 | Insulin receptor, insulin receptor substrate-1, Raf-1, and Mek-1 during hormonal hepatocarcinogenesis by intrahepatic pancreatic islet transplantation in diabetic rats. |
| 360 | 15520221 | Thus, we investigated FAHs, HCAs, and HCCs for altered expression of insulin receptor, insulin receptor substrate-1 (IRS-1), Raf-1 and Mek-1. |
| 361 | 15520221 | IRS-1, Raf-1, and Mek-1 proteins were strongly overexpressed in FAHs and tumors, as compared with the unaltered liver tissue. |
| 362 | 15520221 | Insulin receptor, insulin receptor substrate-1, Raf-1, and Mek-1 during hormonal hepatocarcinogenesis by intrahepatic pancreatic islet transplantation in diabetic rats. |
| 363 | 15520221 | Thus, we investigated FAHs, HCAs, and HCCs for altered expression of insulin receptor, insulin receptor substrate-1 (IRS-1), Raf-1 and Mek-1. |
| 364 | 15520221 | IRS-1, Raf-1, and Mek-1 proteins were strongly overexpressed in FAHs and tumors, as compared with the unaltered liver tissue. |
| 365 | 15640073 | [MAP kinase signal pathway in hyperglycemia-induced congenital neural tube defects]. |
| 366 | 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). |
| 367 | 15640073 | Furthermore, activity of RAF-1, an upstream kinase in ERK1/2 signaling cascade, was evaluated by immunoprecipitation assay. |
| 368 | 15640073 | Under rescuing circumstance,activations of ERK1/2 and RAF-1 were increased, and JNK1/2 were decreased. |
| 369 | 15640073 | MAP kinase signal pathway plays a very important role in hyperglycemia induced neural tube defects. |
| 370 | 15640073 | [MAP kinase signal pathway in hyperglycemia-induced congenital neural tube defects]. |
| 371 | 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). |
| 372 | 15640073 | Furthermore, activity of RAF-1, an upstream kinase in ERK1/2 signaling cascade, was evaluated by immunoprecipitation assay. |
| 373 | 15640073 | Under rescuing circumstance,activations of ERK1/2 and RAF-1 were increased, and JNK1/2 were decreased. |
| 374 | 15640073 | MAP kinase signal pathway plays a very important role in hyperglycemia induced neural tube defects. |
| 375 | 16275148 | Novel actions of IGFBP-3 on intracellular signaling pathways of insulin-secreting cells. |
| 376 | 16275148 | We recently reported insulin-like growth factor binding protein-3 (IGFBP-3) as a novel mediator of apoptosis in insulin-secreting cells. |
| 377 | 16275148 | Using the rat insulinoma RINm5F cell line, we report the first studies in insulin-secreting cells that IGFBP-3 selectively suppresses multiple, key intracellular phosphorelays. |
| 378 | 16275148 | By immunoblot, we demonstrate that G(56)G(80)G(81)-IGFBP-3 suppresses phosphorylation of c-raf-MEK-ERK pathway and p38 kinase in time-dependent and dose-dependent manners. |
| 379 | 16275148 | SAPK/JNK signaling was unaffected. |
| 380 | 16275148 | These data delineate several novel intracellular sites of action for IGFBP-3 in insulin-secreting cells. |
| 381 | 16452245 | After low-number islet transplantation (n = 450), the liver acini downstream of the islets show insulin-induced alterations: massive glycogen and/or fat accumulation, translocation of the insulin receptor, decrease in glucose-6-phosphatase activity, increase in expression of insulin-like growth factor (IGF)-I, IGF-II/mannose-6-phosphate receptor, insulin receptor substrate-1, Raf-1, and Mek-1, corresponding to clear cell preneoplastic foci of altered hepatocytes known from chemical hepatocarcinogenesis and identical to that in streptozotocin-diabetic Lewis rats. |
| 382 | 16452245 | After 6 months, many altered liver acini progressed to other types of preneoplasias often accompanied by an overexpression of the glutathione-S transferase (placental form), IGF-I receptor, and transforming growth factor (TGF)-alpha. |
| 383 | 16452245 | Hepatocarcinogenesis is independent from additional genotoxic compounds (i.e., streptozotocin), but is primarily triggered by increased intracellular insulin signaling via pathways associated with cell growth and proliferation, such as the Ras-Raf-mitogen-activated protein kinase pathway and the IGF system, and secondarily involves other growth factors, such as TGF-alpha. |
| 384 | 16504566 | Raf-1 protein-serine/threonine kinase serves as a central switch board in the transmission of many growth and developmental signals. |
| 385 | 16504566 | We observed that a rapid and detectable decrease in Raf-1 protein levels was induced by methylglyoxal, which was accelerated by treating with a Raf-1 activator, phorbol-12-myristate-13-acetate, and by expressing active forms of Raf-1 and Ras. |
| 386 | 16504566 | Blocking phosphorylation with the protein kinase C inhibitor bisindolylmaleimide, or inhibiting intracellular oxidation by addition of the antioxidant N-acetyl-l-cysteine could reverse the ubiquitination and downregulation of Raf-1 induced by methylglyoxal and phorbol-12-myristate-13-acetate. |
| 387 | 16504566 | These results suggest that methylglyoxal-mediated intracellular oxidation and ubiquitin/proteasome-dependent proteolysis are involved in the downregulation of Raf-1, which may be closely related to the development complications in diabetes. |
| 388 | 16504566 | Raf-1 protein-serine/threonine kinase serves as a central switch board in the transmission of many growth and developmental signals. |
| 389 | 16504566 | We observed that a rapid and detectable decrease in Raf-1 protein levels was induced by methylglyoxal, which was accelerated by treating with a Raf-1 activator, phorbol-12-myristate-13-acetate, and by expressing active forms of Raf-1 and Ras. |
| 390 | 16504566 | Blocking phosphorylation with the protein kinase C inhibitor bisindolylmaleimide, or inhibiting intracellular oxidation by addition of the antioxidant N-acetyl-l-cysteine could reverse the ubiquitination and downregulation of Raf-1 induced by methylglyoxal and phorbol-12-myristate-13-acetate. |
| 391 | 16504566 | These results suggest that methylglyoxal-mediated intracellular oxidation and ubiquitin/proteasome-dependent proteolysis are involved in the downregulation of Raf-1, which may be closely related to the development complications in diabetes. |
| 392 | 16504566 | Raf-1 protein-serine/threonine kinase serves as a central switch board in the transmission of many growth and developmental signals. |
| 393 | 16504566 | We observed that a rapid and detectable decrease in Raf-1 protein levels was induced by methylglyoxal, which was accelerated by treating with a Raf-1 activator, phorbol-12-myristate-13-acetate, and by expressing active forms of Raf-1 and Ras. |
| 394 | 16504566 | Blocking phosphorylation with the protein kinase C inhibitor bisindolylmaleimide, or inhibiting intracellular oxidation by addition of the antioxidant N-acetyl-l-cysteine could reverse the ubiquitination and downregulation of Raf-1 induced by methylglyoxal and phorbol-12-myristate-13-acetate. |
| 395 | 16504566 | These results suggest that methylglyoxal-mediated intracellular oxidation and ubiquitin/proteasome-dependent proteolysis are involved in the downregulation of Raf-1, which may be closely related to the development complications in diabetes. |
| 396 | 16504566 | Raf-1 protein-serine/threonine kinase serves as a central switch board in the transmission of many growth and developmental signals. |
| 397 | 16504566 | We observed that a rapid and detectable decrease in Raf-1 protein levels was induced by methylglyoxal, which was accelerated by treating with a Raf-1 activator, phorbol-12-myristate-13-acetate, and by expressing active forms of Raf-1 and Ras. |
| 398 | 16504566 | Blocking phosphorylation with the protein kinase C inhibitor bisindolylmaleimide, or inhibiting intracellular oxidation by addition of the antioxidant N-acetyl-l-cysteine could reverse the ubiquitination and downregulation of Raf-1 induced by methylglyoxal and phorbol-12-myristate-13-acetate. |
| 399 | 16504566 | These results suggest that methylglyoxal-mediated intracellular oxidation and ubiquitin/proteasome-dependent proteolysis are involved in the downregulation of Raf-1, which may be closely related to the development complications in diabetes. |
| 400 | 16601979 | During the next 12-24 months, many peri-insular ductules progressed via tumor-like cystic lesions to large cystic cholangiomas, accompanied by a translocation of the insulin receptor into the cytoplasm and an increase in expression of insulin-related signaling proteins (Insulin-receptor-substrate-1, Raf-1, Mek-1). |
| 401 | 18006502 | Blocking Raf-1 activity using a specific Raf-1 inhibitor or dominant-negative Raf-1 mutants led to a time- and dose-dependent increase in cell death, assessed by real-time imaging of propidium iodide incorporation, TUNEL, PCR-enhanced DNA laddering, and Caspase-3 cleavage. |
| 402 | 18006502 | Inhibiting Raf-1 in beta-cells led to a striking loss of Bad phosphorylation at serine 112 and an increase in the protein levels of both Bad and Bax. |
| 403 | 18006502 | Conversely, acutely inhibiting phosphatidylinositol 3-kinase Akt had more modest effects on beta-cell death. |
| 404 | 18006502 | Blocking Raf-1 activity using a specific Raf-1 inhibitor or dominant-negative Raf-1 mutants led to a time- and dose-dependent increase in cell death, assessed by real-time imaging of propidium iodide incorporation, TUNEL, PCR-enhanced DNA laddering, and Caspase-3 cleavage. |
| 405 | 18006502 | Inhibiting Raf-1 in beta-cells led to a striking loss of Bad phosphorylation at serine 112 and an increase in the protein levels of both Bad and Bax. |
| 406 | 18006502 | Conversely, acutely inhibiting phosphatidylinositol 3-kinase Akt had more modest effects on beta-cell death. |
| 407 | 18202127 | Insulin stimulates primary beta-cell proliferation via Raf-1 kinase. |
| 408 | 18202127 | Elevating glucose from 5-15 mm did not significantly increase beta-cell replication. beta-Cell proliferation was inhibited by somatostatin as well as inhibitors of insulin signaling. |
| 409 | 18202127 | Interestingly, inhibiting Raf-1 kinase blocked proliferation stimulated by low, but not high (superphysiological), insulin doses. |
| 410 | 18202127 | Insulin-stimulated mouse insulinoma cell proliferation was dependent on both phosphatidylinositol 3-kinase/Akt and Raf-1/MAPK kinase pathways. |
| 411 | 18202127 | Overexpression of Raf-1 was sufficient to increase proliferation in the absence of insulin, whereas a dominant-negative Raf-1 reduced proliferation in the presence of 200-pm insulin. |
| 412 | 18202127 | Together, these results demonstrate for the first time that insulin, at levels that have been measured in vivo, can directly stimulate beta-cell proliferation and that Raf-1 kinase is involved in this process. |
| 413 | 18202127 | Insulin stimulates primary beta-cell proliferation via Raf-1 kinase. |
| 414 | 18202127 | Elevating glucose from 5-15 mm did not significantly increase beta-cell replication. beta-Cell proliferation was inhibited by somatostatin as well as inhibitors of insulin signaling. |
| 415 | 18202127 | Interestingly, inhibiting Raf-1 kinase blocked proliferation stimulated by low, but not high (superphysiological), insulin doses. |
| 416 | 18202127 | Insulin-stimulated mouse insulinoma cell proliferation was dependent on both phosphatidylinositol 3-kinase/Akt and Raf-1/MAPK kinase pathways. |
| 417 | 18202127 | Overexpression of Raf-1 was sufficient to increase proliferation in the absence of insulin, whereas a dominant-negative Raf-1 reduced proliferation in the presence of 200-pm insulin. |
| 418 | 18202127 | Together, these results demonstrate for the first time that insulin, at levels that have been measured in vivo, can directly stimulate beta-cell proliferation and that Raf-1 kinase is involved in this process. |
| 419 | 18202127 | Insulin stimulates primary beta-cell proliferation via Raf-1 kinase. |
| 420 | 18202127 | Elevating glucose from 5-15 mm did not significantly increase beta-cell replication. beta-Cell proliferation was inhibited by somatostatin as well as inhibitors of insulin signaling. |
| 421 | 18202127 | Interestingly, inhibiting Raf-1 kinase blocked proliferation stimulated by low, but not high (superphysiological), insulin doses. |
| 422 | 18202127 | Insulin-stimulated mouse insulinoma cell proliferation was dependent on both phosphatidylinositol 3-kinase/Akt and Raf-1/MAPK kinase pathways. |
| 423 | 18202127 | Overexpression of Raf-1 was sufficient to increase proliferation in the absence of insulin, whereas a dominant-negative Raf-1 reduced proliferation in the presence of 200-pm insulin. |
| 424 | 18202127 | Together, these results demonstrate for the first time that insulin, at levels that have been measured in vivo, can directly stimulate beta-cell proliferation and that Raf-1 kinase is involved in this process. |
| 425 | 18202127 | Insulin stimulates primary beta-cell proliferation via Raf-1 kinase. |
| 426 | 18202127 | Elevating glucose from 5-15 mm did not significantly increase beta-cell replication. beta-Cell proliferation was inhibited by somatostatin as well as inhibitors of insulin signaling. |
| 427 | 18202127 | Interestingly, inhibiting Raf-1 kinase blocked proliferation stimulated by low, but not high (superphysiological), insulin doses. |
| 428 | 18202127 | Insulin-stimulated mouse insulinoma cell proliferation was dependent on both phosphatidylinositol 3-kinase/Akt and Raf-1/MAPK kinase pathways. |
| 429 | 18202127 | Overexpression of Raf-1 was sufficient to increase proliferation in the absence of insulin, whereas a dominant-negative Raf-1 reduced proliferation in the presence of 200-pm insulin. |
| 430 | 18202127 | Together, these results demonstrate for the first time that insulin, at levels that have been measured in vivo, can directly stimulate beta-cell proliferation and that Raf-1 kinase is involved in this process. |
| 431 | 18202127 | Insulin stimulates primary beta-cell proliferation via Raf-1 kinase. |
| 432 | 18202127 | Elevating glucose from 5-15 mm did not significantly increase beta-cell replication. beta-Cell proliferation was inhibited by somatostatin as well as inhibitors of insulin signaling. |
| 433 | 18202127 | Interestingly, inhibiting Raf-1 kinase blocked proliferation stimulated by low, but not high (superphysiological), insulin doses. |
| 434 | 18202127 | Insulin-stimulated mouse insulinoma cell proliferation was dependent on both phosphatidylinositol 3-kinase/Akt and Raf-1/MAPK kinase pathways. |
| 435 | 18202127 | Overexpression of Raf-1 was sufficient to increase proliferation in the absence of insulin, whereas a dominant-negative Raf-1 reduced proliferation in the presence of 200-pm insulin. |
| 436 | 18202127 | Together, these results demonstrate for the first time that insulin, at levels that have been measured in vivo, can directly stimulate beta-cell proliferation and that Raf-1 kinase is involved in this process. |
| 437 | 18418065 | In particular, we highlight the emerging role for Raf-1 kinase in autocrine insulin signaling and beta-cell fate decisions. |
| 438 | 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). |
| 439 | 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%. |
| 440 | 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). |
| 441 | 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%. |
| 442 | 19950198 | Detailed pharmacological analysis demonstrated that insulin-induced A(1)-AR and A(2A)-AR mRNA expression through the Ras/Raf-1/MEK/ERK pathway. |
| 443 | 19950198 | The insulin effect on A(2B)-AR expression was blocked by p38 MAP kinase inhibitor (SB 203580). |
| 444 | 20335317 | The pcDNA3.1-RSOR/MIOX transfectants had an increased NADH/NAD(+) ratio, PKC and TGF-beta activity, Raf1:Ras association, and p-ERK phosphorylation. |
| 445 | 20335317 | These changes were significantly reduced by the inhibitors of PKC, aldose reductase, Ras farnesylation, and MEK1. |
| 446 | 20335317 | Expression of E-cadherin and vimentin paralleled in cells overexpressing RSOR/MIOX or subjected to high-glucose ambience. |
| 447 | 20444941 | Regulation of (pro)renin receptor expression by glucose-induced mitogen-activated protein kinase, nuclear factor-kappaB, and activator protein-1 signaling pathways. |
| 448 | 20444941 | Renal (pro)renin receptor (PRR) expression is increased in diabetes. |
| 449 | 20444941 | We hypothesized that high glucose up-regulates PRR through protein kinase C (PKC)-Raf-ERK and PKC-c-Jun N-terminal kinase (JNK)-c-Jun signaling pathways. |
| 450 | 20444941 | Rat mesangial cells exposed to 30 mm d-glucose demonstrated significant increase in PRR mRNA and protein expression, intracellular phosphorylation of Raf-1 (Y340/341), ERK, JNK, nuclear factor-kappaB (NF-kappaB) p65 (S536) and c-Jun (S63). |
| 451 | 20444941 | By chromatin immunoprecipitation assay and EMSA, high glucose induced more functional NF-kappaB and activator protein (AP)-1 dimers bound to corresponding cis-regulatory elements in the predicted PRR promoter to up-regulate PRR transcription. |
| 452 | 20444941 | Conventional and novel PKC inhibitors Chelerythrine and Rottlerin, Raf-1 inhibitor GW5074, MEK1/2 inhibitor U0126, JNK inhibitor SP600125, NF-kappaB inhibitor Quinazoline, and AP-1 inhibitor Curcumin, respectively, attenuated glucose-induced PRR up-regulation. |
| 453 | 20444941 | Chelerythrine and Rottlerin also inhibited glucose-induced phosphorylation of Raf-1 (Y340/341), ERK1/2, JNK, NF-kappaB p65 (S536), and c-Jun (S63). |
| 454 | 20444941 | GW5074 and U0126 inhibited the phosphorylation of ERK1/2 and NF-kappaB p65 (S536). |
| 455 | 20444941 | SP600125 inhibited phosphorylation of NF-kappaB p65 (S536) and c-Jun (S63). |
| 456 | 20444941 | We conclude that high glucose up-regulates the expression of PRR through mechanisms dependent on both PKC-Raf-ERK and PKC-JNK-c-Jun signaling pathways. |
| 457 | 20444941 | NF-kappaB and AP-1 are involved in high-glucose-induced PRR up-regulation in rat mesangial cells. |
| 458 | 20444941 | Regulation of (pro)renin receptor expression by glucose-induced mitogen-activated protein kinase, nuclear factor-kappaB, and activator protein-1 signaling pathways. |
| 459 | 20444941 | Renal (pro)renin receptor (PRR) expression is increased in diabetes. |
| 460 | 20444941 | We hypothesized that high glucose up-regulates PRR through protein kinase C (PKC)-Raf-ERK and PKC-c-Jun N-terminal kinase (JNK)-c-Jun signaling pathways. |
| 461 | 20444941 | Rat mesangial cells exposed to 30 mm d-glucose demonstrated significant increase in PRR mRNA and protein expression, intracellular phosphorylation of Raf-1 (Y340/341), ERK, JNK, nuclear factor-kappaB (NF-kappaB) p65 (S536) and c-Jun (S63). |
| 462 | 20444941 | By chromatin immunoprecipitation assay and EMSA, high glucose induced more functional NF-kappaB and activator protein (AP)-1 dimers bound to corresponding cis-regulatory elements in the predicted PRR promoter to up-regulate PRR transcription. |
| 463 | 20444941 | Conventional and novel PKC inhibitors Chelerythrine and Rottlerin, Raf-1 inhibitor GW5074, MEK1/2 inhibitor U0126, JNK inhibitor SP600125, NF-kappaB inhibitor Quinazoline, and AP-1 inhibitor Curcumin, respectively, attenuated glucose-induced PRR up-regulation. |
| 464 | 20444941 | Chelerythrine and Rottlerin also inhibited glucose-induced phosphorylation of Raf-1 (Y340/341), ERK1/2, JNK, NF-kappaB p65 (S536), and c-Jun (S63). |
| 465 | 20444941 | GW5074 and U0126 inhibited the phosphorylation of ERK1/2 and NF-kappaB p65 (S536). |
| 466 | 20444941 | SP600125 inhibited phosphorylation of NF-kappaB p65 (S536) and c-Jun (S63). |
| 467 | 20444941 | We conclude that high glucose up-regulates the expression of PRR through mechanisms dependent on both PKC-Raf-ERK and PKC-JNK-c-Jun signaling pathways. |
| 468 | 20444941 | NF-kappaB and AP-1 are involved in high-glucose-induced PRR up-regulation in rat mesangial cells. |
| 469 | 20444941 | Regulation of (pro)renin receptor expression by glucose-induced mitogen-activated protein kinase, nuclear factor-kappaB, and activator protein-1 signaling pathways. |
| 470 | 20444941 | Renal (pro)renin receptor (PRR) expression is increased in diabetes. |
| 471 | 20444941 | We hypothesized that high glucose up-regulates PRR through protein kinase C (PKC)-Raf-ERK and PKC-c-Jun N-terminal kinase (JNK)-c-Jun signaling pathways. |
| 472 | 20444941 | Rat mesangial cells exposed to 30 mm d-glucose demonstrated significant increase in PRR mRNA and protein expression, intracellular phosphorylation of Raf-1 (Y340/341), ERK, JNK, nuclear factor-kappaB (NF-kappaB) p65 (S536) and c-Jun (S63). |
| 473 | 20444941 | By chromatin immunoprecipitation assay and EMSA, high glucose induced more functional NF-kappaB and activator protein (AP)-1 dimers bound to corresponding cis-regulatory elements in the predicted PRR promoter to up-regulate PRR transcription. |
| 474 | 20444941 | Conventional and novel PKC inhibitors Chelerythrine and Rottlerin, Raf-1 inhibitor GW5074, MEK1/2 inhibitor U0126, JNK inhibitor SP600125, NF-kappaB inhibitor Quinazoline, and AP-1 inhibitor Curcumin, respectively, attenuated glucose-induced PRR up-regulation. |
| 475 | 20444941 | Chelerythrine and Rottlerin also inhibited glucose-induced phosphorylation of Raf-1 (Y340/341), ERK1/2, JNK, NF-kappaB p65 (S536), and c-Jun (S63). |
| 476 | 20444941 | GW5074 and U0126 inhibited the phosphorylation of ERK1/2 and NF-kappaB p65 (S536). |
| 477 | 20444941 | SP600125 inhibited phosphorylation of NF-kappaB p65 (S536) and c-Jun (S63). |
| 478 | 20444941 | We conclude that high glucose up-regulates the expression of PRR through mechanisms dependent on both PKC-Raf-ERK and PKC-JNK-c-Jun signaling pathways. |
| 479 | 20444941 | NF-kappaB and AP-1 are involved in high-glucose-induced PRR up-regulation in rat mesangial cells. |
| 480 | 20630999 | Involvement of RAGE, NADPH oxidase, and Ras/Raf-1 pathway in glycated LDL-induced expression of heat shock factor-1 and plasminogen activator inhibitor-1 in vascular endothelial cells. |
| 481 | 20630999 | Previous studies in our laboratory demonstrated that heat shock factor-1 (HSF1) is involved in glyLDL-induced PAI-1 overproduction in vascular endothelial cells (EC). |
| 482 | 20630999 | The present study investigated transmembrane signaling mechanisms involved in glyLDL-induced HSF1 and PAI-1 up-regulation in cultured human vascular EC and streptozotocin-induced diabetic mice. |
| 483 | 20630999 | Farnesyltransferase inhibitor-277 or small interference RNA against H-Ras inhibited glyLDL-induced increases in HSF1 and PAI-1 in EC. |
| 484 | 20630999 | Treatment with diphenyleneiodonium, a nicotinamide adenine dinucleotide phosphate oxidase (NOX) inhibitor, blocked glyLDL-induced translocation of H-Ras, elevated abundances of HSF1 and PAI-1 in EC, and increased release of hydrogen peroxide from EC. |
| 485 | 20630999 | Small interference RNA for p22(phox) prevented glyLDL-induced expression of NOX2, HSF1, and PAI-1 in EC. |
| 486 | 20630999 | GlyLDL significantly increased V-raf-1 murine leukemia viral oncogene homolog 1 (Raf-1) phosphorylation. |
| 487 | 20630999 | Treatment with Raf-1 inhibitor blocked glyLDL-induced increase of PAI-1 mRNA in EC. |
| 488 | 20630999 | The levels of RAGE, H-Ras, NOX4, HSF1, and PAI-1 were increased in hearts of streptozotocin-diabetic mice and positively correlated with plasma glucose. |
| 489 | 20630999 | The results suggest that RAGE, NOX, and H-Ras/Raf-1 are implicated in the up-regulation of HSF1 or PAI-1 in vascular EC under diabetes-associated metabolic stress. |
| 490 | 20630999 | Involvement of RAGE, NADPH oxidase, and Ras/Raf-1 pathway in glycated LDL-induced expression of heat shock factor-1 and plasminogen activator inhibitor-1 in vascular endothelial cells. |
| 491 | 20630999 | Previous studies in our laboratory demonstrated that heat shock factor-1 (HSF1) is involved in glyLDL-induced PAI-1 overproduction in vascular endothelial cells (EC). |
| 492 | 20630999 | The present study investigated transmembrane signaling mechanisms involved in glyLDL-induced HSF1 and PAI-1 up-regulation in cultured human vascular EC and streptozotocin-induced diabetic mice. |
| 493 | 20630999 | Farnesyltransferase inhibitor-277 or small interference RNA against H-Ras inhibited glyLDL-induced increases in HSF1 and PAI-1 in EC. |
| 494 | 20630999 | Treatment with diphenyleneiodonium, a nicotinamide adenine dinucleotide phosphate oxidase (NOX) inhibitor, blocked glyLDL-induced translocation of H-Ras, elevated abundances of HSF1 and PAI-1 in EC, and increased release of hydrogen peroxide from EC. |
| 495 | 20630999 | Small interference RNA for p22(phox) prevented glyLDL-induced expression of NOX2, HSF1, and PAI-1 in EC. |
| 496 | 20630999 | GlyLDL significantly increased V-raf-1 murine leukemia viral oncogene homolog 1 (Raf-1) phosphorylation. |
| 497 | 20630999 | Treatment with Raf-1 inhibitor blocked glyLDL-induced increase of PAI-1 mRNA in EC. |
| 498 | 20630999 | The levels of RAGE, H-Ras, NOX4, HSF1, and PAI-1 were increased in hearts of streptozotocin-diabetic mice and positively correlated with plasma glucose. |
| 499 | 20630999 | The results suggest that RAGE, NOX, and H-Ras/Raf-1 are implicated in the up-regulation of HSF1 or PAI-1 in vascular EC under diabetes-associated metabolic stress. |
| 500 | 20630999 | Involvement of RAGE, NADPH oxidase, and Ras/Raf-1 pathway in glycated LDL-induced expression of heat shock factor-1 and plasminogen activator inhibitor-1 in vascular endothelial cells. |
| 501 | 20630999 | Previous studies in our laboratory demonstrated that heat shock factor-1 (HSF1) is involved in glyLDL-induced PAI-1 overproduction in vascular endothelial cells (EC). |
| 502 | 20630999 | The present study investigated transmembrane signaling mechanisms involved in glyLDL-induced HSF1 and PAI-1 up-regulation in cultured human vascular EC and streptozotocin-induced diabetic mice. |
| 503 | 20630999 | Farnesyltransferase inhibitor-277 or small interference RNA against H-Ras inhibited glyLDL-induced increases in HSF1 and PAI-1 in EC. |
| 504 | 20630999 | Treatment with diphenyleneiodonium, a nicotinamide adenine dinucleotide phosphate oxidase (NOX) inhibitor, blocked glyLDL-induced translocation of H-Ras, elevated abundances of HSF1 and PAI-1 in EC, and increased release of hydrogen peroxide from EC. |
| 505 | 20630999 | Small interference RNA for p22(phox) prevented glyLDL-induced expression of NOX2, HSF1, and PAI-1 in EC. |
| 506 | 20630999 | GlyLDL significantly increased V-raf-1 murine leukemia viral oncogene homolog 1 (Raf-1) phosphorylation. |
| 507 | 20630999 | Treatment with Raf-1 inhibitor blocked glyLDL-induced increase of PAI-1 mRNA in EC. |
| 508 | 20630999 | The levels of RAGE, H-Ras, NOX4, HSF1, and PAI-1 were increased in hearts of streptozotocin-diabetic mice and positively correlated with plasma glucose. |
| 509 | 20630999 | The results suggest that RAGE, NOX, and H-Ras/Raf-1 are implicated in the up-regulation of HSF1 or PAI-1 in vascular EC under diabetes-associated metabolic stress. |
| 510 | 20630999 | Involvement of RAGE, NADPH oxidase, and Ras/Raf-1 pathway in glycated LDL-induced expression of heat shock factor-1 and plasminogen activator inhibitor-1 in vascular endothelial cells. |
| 511 | 20630999 | Previous studies in our laboratory demonstrated that heat shock factor-1 (HSF1) is involved in glyLDL-induced PAI-1 overproduction in vascular endothelial cells (EC). |
| 512 | 20630999 | The present study investigated transmembrane signaling mechanisms involved in glyLDL-induced HSF1 and PAI-1 up-regulation in cultured human vascular EC and streptozotocin-induced diabetic mice. |
| 513 | 20630999 | Farnesyltransferase inhibitor-277 or small interference RNA against H-Ras inhibited glyLDL-induced increases in HSF1 and PAI-1 in EC. |
| 514 | 20630999 | Treatment with diphenyleneiodonium, a nicotinamide adenine dinucleotide phosphate oxidase (NOX) inhibitor, blocked glyLDL-induced translocation of H-Ras, elevated abundances of HSF1 and PAI-1 in EC, and increased release of hydrogen peroxide from EC. |
| 515 | 20630999 | Small interference RNA for p22(phox) prevented glyLDL-induced expression of NOX2, HSF1, and PAI-1 in EC. |
| 516 | 20630999 | GlyLDL significantly increased V-raf-1 murine leukemia viral oncogene homolog 1 (Raf-1) phosphorylation. |
| 517 | 20630999 | Treatment with Raf-1 inhibitor blocked glyLDL-induced increase of PAI-1 mRNA in EC. |
| 518 | 20630999 | The levels of RAGE, H-Ras, NOX4, HSF1, and PAI-1 were increased in hearts of streptozotocin-diabetic mice and positively correlated with plasma glucose. |
| 519 | 20630999 | The results suggest that RAGE, NOX, and H-Ras/Raf-1 are implicated in the up-regulation of HSF1 or PAI-1 in vascular EC under diabetes-associated metabolic stress. |
| 520 | 21567393 | Using isolated retinal endothelial cells, the effect of regulation of H-Ras downstream signaling cascade, Raf-1, MEK, and ERK, was investigated on glucose-induced activation of MMP9. |
| 521 | 21567393 | Regulation of Raf-1/MEK/ERK by their specific siRNAs and pharmacologic inhibitors prevented glucose-induced activation of MMP9 in retinal endothelial cells. |
| 522 | 21567393 | In MMP9-KO mice, diabetes had no effect on retinal MMP9 activation, and H-Ras/Raf-1/MEK signaling cascade remained normal. |
| 523 | 21567393 | Similarly, donors with diabetic retinopathy had increased MMP9 activity in their retinal microvessels, the site of histopathology associated with diabetic retinopathy, and this was accompanied by activated H-Ras signaling pathway (Raf-1/ERK). |
| 524 | 21567393 | Collectively, these results suggest that Ras/Raf-1/MEK/ERK cascade has an important role in the activation of retinal MMP9 resulting in the apoptosis of its capillary cells. |
| 525 | 21567393 | Using isolated retinal endothelial cells, the effect of regulation of H-Ras downstream signaling cascade, Raf-1, MEK, and ERK, was investigated on glucose-induced activation of MMP9. |
| 526 | 21567393 | Regulation of Raf-1/MEK/ERK by their specific siRNAs and pharmacologic inhibitors prevented glucose-induced activation of MMP9 in retinal endothelial cells. |
| 527 | 21567393 | In MMP9-KO mice, diabetes had no effect on retinal MMP9 activation, and H-Ras/Raf-1/MEK signaling cascade remained normal. |
| 528 | 21567393 | Similarly, donors with diabetic retinopathy had increased MMP9 activity in their retinal microvessels, the site of histopathology associated with diabetic retinopathy, and this was accompanied by activated H-Ras signaling pathway (Raf-1/ERK). |
| 529 | 21567393 | Collectively, these results suggest that Ras/Raf-1/MEK/ERK cascade has an important role in the activation of retinal MMP9 resulting in the apoptosis of its capillary cells. |
| 530 | 21567393 | Using isolated retinal endothelial cells, the effect of regulation of H-Ras downstream signaling cascade, Raf-1, MEK, and ERK, was investigated on glucose-induced activation of MMP9. |
| 531 | 21567393 | Regulation of Raf-1/MEK/ERK by their specific siRNAs and pharmacologic inhibitors prevented glucose-induced activation of MMP9 in retinal endothelial cells. |
| 532 | 21567393 | In MMP9-KO mice, diabetes had no effect on retinal MMP9 activation, and H-Ras/Raf-1/MEK signaling cascade remained normal. |
| 533 | 21567393 | Similarly, donors with diabetic retinopathy had increased MMP9 activity in their retinal microvessels, the site of histopathology associated with diabetic retinopathy, and this was accompanied by activated H-Ras signaling pathway (Raf-1/ERK). |
| 534 | 21567393 | Collectively, these results suggest that Ras/Raf-1/MEK/ERK cascade has an important role in the activation of retinal MMP9 resulting in the apoptosis of its capillary cells. |
| 535 | 21567393 | Using isolated retinal endothelial cells, the effect of regulation of H-Ras downstream signaling cascade, Raf-1, MEK, and ERK, was investigated on glucose-induced activation of MMP9. |
| 536 | 21567393 | Regulation of Raf-1/MEK/ERK by their specific siRNAs and pharmacologic inhibitors prevented glucose-induced activation of MMP9 in retinal endothelial cells. |
| 537 | 21567393 | In MMP9-KO mice, diabetes had no effect on retinal MMP9 activation, and H-Ras/Raf-1/MEK signaling cascade remained normal. |
| 538 | 21567393 | Similarly, donors with diabetic retinopathy had increased MMP9 activity in their retinal microvessels, the site of histopathology associated with diabetic retinopathy, and this was accompanied by activated H-Ras signaling pathway (Raf-1/ERK). |
| 539 | 21567393 | Collectively, these results suggest that Ras/Raf-1/MEK/ERK cascade has an important role in the activation of retinal MMP9 resulting in the apoptosis of its capillary cells. |
| 540 | 21567393 | Using isolated retinal endothelial cells, the effect of regulation of H-Ras downstream signaling cascade, Raf-1, MEK, and ERK, was investigated on glucose-induced activation of MMP9. |
| 541 | 21567393 | Regulation of Raf-1/MEK/ERK by their specific siRNAs and pharmacologic inhibitors prevented glucose-induced activation of MMP9 in retinal endothelial cells. |
| 542 | 21567393 | In MMP9-KO mice, diabetes had no effect on retinal MMP9 activation, and H-Ras/Raf-1/MEK signaling cascade remained normal. |
| 543 | 21567393 | Similarly, donors with diabetic retinopathy had increased MMP9 activity in their retinal microvessels, the site of histopathology associated with diabetic retinopathy, and this was accompanied by activated H-Ras signaling pathway (Raf-1/ERK). |
| 544 | 21567393 | Collectively, these results suggest that Ras/Raf-1/MEK/ERK cascade has an important role in the activation of retinal MMP9 resulting in the apoptosis of its capillary cells. |
| 545 | 21817126 | Pancreatic β-cell Raf-1 is required for glucose tolerance, insulin secretion, and insulin 2 transcription. |
| 546 | 21817126 | We have previously reported that insulin protects β cells from apoptosis and promotes proliferation by activating Raf-1 signaling in cultured human islets, mouse islets, and MIN6 cells. |
| 547 | 21817126 | As Raf-1 activity is critical for basal apoptosis and insulin secretion in vitro, we hypothesized that Raf-1 may play an important role in glucose homeostasis in vivo. |
| 548 | 21817126 | RIPCre(+/+):Raf-1(flox/flox) mice had increased fasting blood glucose levels and impaired glucose tolerance but normal insulin tolerance compared to littermate controls. |
| 549 | 21817126 | However, islet insulin protein and insulin 2 mRNA, but not insulin 1 mRNA, were dramatically reduced in Raf-1-knockout mice. |
| 550 | 21817126 | Our data further indicate that Raf-1 specifically and acutely regulates insulin 2 mRNA via negative action on Foxo1, which has been shown to selectively control the insulin 2 gene. |
| 551 | 21817126 | This work provides the first direct evidence that Raf-1 signaling is essential for the regulation of basal insulin transcription and the supply of releasable insulin in vivo. |
| 552 | 21817126 | Pancreatic β-cell Raf-1 is required for glucose tolerance, insulin secretion, and insulin 2 transcription. |
| 553 | 21817126 | We have previously reported that insulin protects β cells from apoptosis and promotes proliferation by activating Raf-1 signaling in cultured human islets, mouse islets, and MIN6 cells. |
| 554 | 21817126 | As Raf-1 activity is critical for basal apoptosis and insulin secretion in vitro, we hypothesized that Raf-1 may play an important role in glucose homeostasis in vivo. |
| 555 | 21817126 | RIPCre(+/+):Raf-1(flox/flox) mice had increased fasting blood glucose levels and impaired glucose tolerance but normal insulin tolerance compared to littermate controls. |
| 556 | 21817126 | However, islet insulin protein and insulin 2 mRNA, but not insulin 1 mRNA, were dramatically reduced in Raf-1-knockout mice. |
| 557 | 21817126 | Our data further indicate that Raf-1 specifically and acutely regulates insulin 2 mRNA via negative action on Foxo1, which has been shown to selectively control the insulin 2 gene. |
| 558 | 21817126 | This work provides the first direct evidence that Raf-1 signaling is essential for the regulation of basal insulin transcription and the supply of releasable insulin in vivo. |
| 559 | 21817126 | Pancreatic β-cell Raf-1 is required for glucose tolerance, insulin secretion, and insulin 2 transcription. |
| 560 | 21817126 | We have previously reported that insulin protects β cells from apoptosis and promotes proliferation by activating Raf-1 signaling in cultured human islets, mouse islets, and MIN6 cells. |
| 561 | 21817126 | As Raf-1 activity is critical for basal apoptosis and insulin secretion in vitro, we hypothesized that Raf-1 may play an important role in glucose homeostasis in vivo. |
| 562 | 21817126 | RIPCre(+/+):Raf-1(flox/flox) mice had increased fasting blood glucose levels and impaired glucose tolerance but normal insulin tolerance compared to littermate controls. |
| 563 | 21817126 | However, islet insulin protein and insulin 2 mRNA, but not insulin 1 mRNA, were dramatically reduced in Raf-1-knockout mice. |
| 564 | 21817126 | Our data further indicate that Raf-1 specifically and acutely regulates insulin 2 mRNA via negative action on Foxo1, which has been shown to selectively control the insulin 2 gene. |
| 565 | 21817126 | This work provides the first direct evidence that Raf-1 signaling is essential for the regulation of basal insulin transcription and the supply of releasable insulin in vivo. |
| 566 | 21817126 | Pancreatic β-cell Raf-1 is required for glucose tolerance, insulin secretion, and insulin 2 transcription. |
| 567 | 21817126 | We have previously reported that insulin protects β cells from apoptosis and promotes proliferation by activating Raf-1 signaling in cultured human islets, mouse islets, and MIN6 cells. |
| 568 | 21817126 | As Raf-1 activity is critical for basal apoptosis and insulin secretion in vitro, we hypothesized that Raf-1 may play an important role in glucose homeostasis in vivo. |
| 569 | 21817126 | RIPCre(+/+):Raf-1(flox/flox) mice had increased fasting blood glucose levels and impaired glucose tolerance but normal insulin tolerance compared to littermate controls. |
| 570 | 21817126 | However, islet insulin protein and insulin 2 mRNA, but not insulin 1 mRNA, were dramatically reduced in Raf-1-knockout mice. |
| 571 | 21817126 | Our data further indicate that Raf-1 specifically and acutely regulates insulin 2 mRNA via negative action on Foxo1, which has been shown to selectively control the insulin 2 gene. |
| 572 | 21817126 | This work provides the first direct evidence that Raf-1 signaling is essential for the regulation of basal insulin transcription and the supply of releasable insulin in vivo. |
| 573 | 21817126 | Pancreatic β-cell Raf-1 is required for glucose tolerance, insulin secretion, and insulin 2 transcription. |
| 574 | 21817126 | We have previously reported that insulin protects β cells from apoptosis and promotes proliferation by activating Raf-1 signaling in cultured human islets, mouse islets, and MIN6 cells. |
| 575 | 21817126 | As Raf-1 activity is critical for basal apoptosis and insulin secretion in vitro, we hypothesized that Raf-1 may play an important role in glucose homeostasis in vivo. |
| 576 | 21817126 | RIPCre(+/+):Raf-1(flox/flox) mice had increased fasting blood glucose levels and impaired glucose tolerance but normal insulin tolerance compared to littermate controls. |
| 577 | 21817126 | However, islet insulin protein and insulin 2 mRNA, but not insulin 1 mRNA, were dramatically reduced in Raf-1-knockout mice. |
| 578 | 21817126 | Our data further indicate that Raf-1 specifically and acutely regulates insulin 2 mRNA via negative action on Foxo1, which has been shown to selectively control the insulin 2 gene. |
| 579 | 21817126 | This work provides the first direct evidence that Raf-1 signaling is essential for the regulation of basal insulin transcription and the supply of releasable insulin in vivo. |
| 580 | 21817126 | Pancreatic β-cell Raf-1 is required for glucose tolerance, insulin secretion, and insulin 2 transcription. |
| 581 | 21817126 | We have previously reported that insulin protects β cells from apoptosis and promotes proliferation by activating Raf-1 signaling in cultured human islets, mouse islets, and MIN6 cells. |
| 582 | 21817126 | As Raf-1 activity is critical for basal apoptosis and insulin secretion in vitro, we hypothesized that Raf-1 may play an important role in glucose homeostasis in vivo. |
| 583 | 21817126 | RIPCre(+/+):Raf-1(flox/flox) mice had increased fasting blood glucose levels and impaired glucose tolerance but normal insulin tolerance compared to littermate controls. |
| 584 | 21817126 | However, islet insulin protein and insulin 2 mRNA, but not insulin 1 mRNA, were dramatically reduced in Raf-1-knockout mice. |
| 585 | 21817126 | Our data further indicate that Raf-1 specifically and acutely regulates insulin 2 mRNA via negative action on Foxo1, which has been shown to selectively control the insulin 2 gene. |
| 586 | 21817126 | This work provides the first direct evidence that Raf-1 signaling is essential for the regulation of basal insulin transcription and the supply of releasable insulin in vivo. |
| 587 | 21817126 | Pancreatic β-cell Raf-1 is required for glucose tolerance, insulin secretion, and insulin 2 transcription. |
| 588 | 21817126 | We have previously reported that insulin protects β cells from apoptosis and promotes proliferation by activating Raf-1 signaling in cultured human islets, mouse islets, and MIN6 cells. |
| 589 | 21817126 | As Raf-1 activity is critical for basal apoptosis and insulin secretion in vitro, we hypothesized that Raf-1 may play an important role in glucose homeostasis in vivo. |
| 590 | 21817126 | RIPCre(+/+):Raf-1(flox/flox) mice had increased fasting blood glucose levels and impaired glucose tolerance but normal insulin tolerance compared to littermate controls. |
| 591 | 21817126 | However, islet insulin protein and insulin 2 mRNA, but not insulin 1 mRNA, were dramatically reduced in Raf-1-knockout mice. |
| 592 | 21817126 | Our data further indicate that Raf-1 specifically and acutely regulates insulin 2 mRNA via negative action on Foxo1, which has been shown to selectively control the insulin 2 gene. |
| 593 | 21817126 | This work provides the first direct evidence that Raf-1 signaling is essential for the regulation of basal insulin transcription and the supply of releasable insulin in vivo. |
| 594 | 22826029 | We studied the expression and signaling of GLP-1 receptor (GLP-1R) on glomerular endothelial cells and the novel finding of protein kinase A-dependent phosphorylation of c-Raf at Ser259 and its inhibition of angiotensin II (Ang II) phospho-c-Raf(Ser338) and Erk1/2 phosphorylation. |
| 595 | 22826029 | Ang II and GLP-1 actions in glomerular endothelial cells were analyzed with small interfering RNA of GLP-1R. |
| 596 | 22826029 | PKCβ isoform activation induced by diabetes decreased GLP-1R expression and protective action on the renal endothelium by increasing its degradation via ubiquitination and enhancing phospho-c-Raf(Ser338) and Ang II activation of phospho-Erk1/2. |
| 597 | 22826029 | EC-PKCβ2Tg mice exhibited decreased GLP-1R expression and increased phospho-c-Raf(Ser338), leading to enhanced effects of Ang II. |
| 598 | 22826029 | These results showed that the renal protective effects of GLP-1 were mediated via the inhibition of Ang II actions on cRaf(Ser259) and diminished by diabetes because of PKCβ activation and the increased degradation of GLP-1R in the glomerular endothelial cells. |
| 599 | 22826029 | We studied the expression and signaling of GLP-1 receptor (GLP-1R) on glomerular endothelial cells and the novel finding of protein kinase A-dependent phosphorylation of c-Raf at Ser259 and its inhibition of angiotensin II (Ang II) phospho-c-Raf(Ser338) and Erk1/2 phosphorylation. |
| 600 | 22826029 | Ang II and GLP-1 actions in glomerular endothelial cells were analyzed with small interfering RNA of GLP-1R. |
| 601 | 22826029 | PKCβ isoform activation induced by diabetes decreased GLP-1R expression and protective action on the renal endothelium by increasing its degradation via ubiquitination and enhancing phospho-c-Raf(Ser338) and Ang II activation of phospho-Erk1/2. |
| 602 | 22826029 | EC-PKCβ2Tg mice exhibited decreased GLP-1R expression and increased phospho-c-Raf(Ser338), leading to enhanced effects of Ang II. |
| 603 | 22826029 | These results showed that the renal protective effects of GLP-1 were mediated via the inhibition of Ang II actions on cRaf(Ser259) and diminished by diabetes because of PKCβ activation and the increased degradation of GLP-1R in the glomerular endothelial cells. |
| 604 | 22826029 | We studied the expression and signaling of GLP-1 receptor (GLP-1R) on glomerular endothelial cells and the novel finding of protein kinase A-dependent phosphorylation of c-Raf at Ser259 and its inhibition of angiotensin II (Ang II) phospho-c-Raf(Ser338) and Erk1/2 phosphorylation. |
| 605 | 22826029 | Ang II and GLP-1 actions in glomerular endothelial cells were analyzed with small interfering RNA of GLP-1R. |
| 606 | 22826029 | PKCβ isoform activation induced by diabetes decreased GLP-1R expression and protective action on the renal endothelium by increasing its degradation via ubiquitination and enhancing phospho-c-Raf(Ser338) and Ang II activation of phospho-Erk1/2. |
| 607 | 22826029 | EC-PKCβ2Tg mice exhibited decreased GLP-1R expression and increased phospho-c-Raf(Ser338), leading to enhanced effects of Ang II. |
| 608 | 22826029 | These results showed that the renal protective effects of GLP-1 were mediated via the inhibition of Ang II actions on cRaf(Ser259) and diminished by diabetes because of PKCβ activation and the increased degradation of GLP-1R in the glomerular endothelial cells. |
| 609 | 22983684 | Effects of selenium and exendin-4 on glucagon-like peptide-1 receptor, IRS-1, and Raf-1 in the liver of diabetic rats. |
| 610 | 22983684 | Herein, we investigated their effects on the expression of glucagon-like peptide-1 receptor (GLP-1R), insulin receptor substrate-1 (IRS-1), and Raf-1 in the livers of rats with streptozotocin-induced diabetes. |
| 611 | 22983684 | Induction of diabetes mellitus resulted in decreased level of GLP-1R and increased levels of IRS-1 and Raf-1 in the liver. |
| 612 | 22983684 | Treatment of diabetic rats with selenium or exendin-4 resulted in increased level of GLP-1R and decreased levels of IRS-1 and Raf-1 in the liver, compared with the levels in diabetic rats. |
| 613 | 22983684 | Therefore, the antidiabetic actions of selenium and exendin-4 involve their effects on GLP-1R, IRS-1, and Raf-1 levels in the liver. |
| 614 | 22983684 | Effects of selenium and exendin-4 on glucagon-like peptide-1 receptor, IRS-1, and Raf-1 in the liver of diabetic rats. |
| 615 | 22983684 | Herein, we investigated their effects on the expression of glucagon-like peptide-1 receptor (GLP-1R), insulin receptor substrate-1 (IRS-1), and Raf-1 in the livers of rats with streptozotocin-induced diabetes. |
| 616 | 22983684 | Induction of diabetes mellitus resulted in decreased level of GLP-1R and increased levels of IRS-1 and Raf-1 in the liver. |
| 617 | 22983684 | Treatment of diabetic rats with selenium or exendin-4 resulted in increased level of GLP-1R and decreased levels of IRS-1 and Raf-1 in the liver, compared with the levels in diabetic rats. |
| 618 | 22983684 | Therefore, the antidiabetic actions of selenium and exendin-4 involve their effects on GLP-1R, IRS-1, and Raf-1 levels in the liver. |
| 619 | 22983684 | Effects of selenium and exendin-4 on glucagon-like peptide-1 receptor, IRS-1, and Raf-1 in the liver of diabetic rats. |
| 620 | 22983684 | Herein, we investigated their effects on the expression of glucagon-like peptide-1 receptor (GLP-1R), insulin receptor substrate-1 (IRS-1), and Raf-1 in the livers of rats with streptozotocin-induced diabetes. |
| 621 | 22983684 | Induction of diabetes mellitus resulted in decreased level of GLP-1R and increased levels of IRS-1 and Raf-1 in the liver. |
| 622 | 22983684 | Treatment of diabetic rats with selenium or exendin-4 resulted in increased level of GLP-1R and decreased levels of IRS-1 and Raf-1 in the liver, compared with the levels in diabetic rats. |
| 623 | 22983684 | Therefore, the antidiabetic actions of selenium and exendin-4 involve their effects on GLP-1R, IRS-1, and Raf-1 levels in the liver. |
| 624 | 22983684 | Effects of selenium and exendin-4 on glucagon-like peptide-1 receptor, IRS-1, and Raf-1 in the liver of diabetic rats. |
| 625 | 22983684 | Herein, we investigated their effects on the expression of glucagon-like peptide-1 receptor (GLP-1R), insulin receptor substrate-1 (IRS-1), and Raf-1 in the livers of rats with streptozotocin-induced diabetes. |
| 626 | 22983684 | Induction of diabetes mellitus resulted in decreased level of GLP-1R and increased levels of IRS-1 and Raf-1 in the liver. |
| 627 | 22983684 | Treatment of diabetic rats with selenium or exendin-4 resulted in increased level of GLP-1R and decreased levels of IRS-1 and Raf-1 in the liver, compared with the levels in diabetic rats. |
| 628 | 22983684 | Therefore, the antidiabetic actions of selenium and exendin-4 involve their effects on GLP-1R, IRS-1, and Raf-1 levels in the liver. |
| 629 | 22983684 | Effects of selenium and exendin-4 on glucagon-like peptide-1 receptor, IRS-1, and Raf-1 in the liver of diabetic rats. |
| 630 | 22983684 | Herein, we investigated their effects on the expression of glucagon-like peptide-1 receptor (GLP-1R), insulin receptor substrate-1 (IRS-1), and Raf-1 in the livers of rats with streptozotocin-induced diabetes. |
| 631 | 22983684 | Induction of diabetes mellitus resulted in decreased level of GLP-1R and increased levels of IRS-1 and Raf-1 in the liver. |
| 632 | 22983684 | Treatment of diabetic rats with selenium or exendin-4 resulted in increased level of GLP-1R and decreased levels of IRS-1 and Raf-1 in the liver, compared with the levels in diabetic rats. |
| 633 | 22983684 | Therefore, the antidiabetic actions of selenium and exendin-4 involve their effects on GLP-1R, IRS-1, and Raf-1 levels in the liver. |
| 634 | 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. |