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Gene Information
Gene symbol: PPP2R4
Gene name: protein phosphatase 2A activator, regulatory subunit 4
HGNC ID: 9308
Synonyms: PTPA, PR53
Related Genes
| # | Gene Symbol | Number of hits |
| 1 | ACACA | 1 hits |
| 2 | ACACB | 1 hits |
| 3 | ADIPOQ | 1 hits |
| 4 | AKT1 | 1 hits |
| 5 | ALPI | 1 hits |
| 6 | ANP32A | 1 hits |
| 7 | APP | 1 hits |
| 8 | BCL2 | 1 hits |
| 9 | CDK5R1 | 1 hits |
| 10 | CKM | 1 hits |
| 11 | CREB1 | 1 hits |
| 12 | CREM | 1 hits |
| 13 | CRTC2 | 1 hits |
| 14 | CSNK2A1 | 1 hits |
| 15 | DNM2 | 1 hits |
| 16 | FOXO1 | 1 hits |
| 17 | HSP90AA1 | 1 hits |
| 18 | IGF1 | 1 hits |
| 19 | INPPL1 | 1 hits |
| 20 | INS | 1 hits |
| 21 | IRS1 | 1 hits |
| 22 | JAK2 | 1 hits |
| 23 | KSR1 | 1 hits |
| 24 | LGMN | 1 hits |
| 25 | MAPK1 | 1 hits |
| 26 | MAPK3 | 1 hits |
| 27 | MAPK6 | 1 hits |
| 28 | MAPT | 1 hits |
| 29 | MINK1 | 1 hits |
| 30 | MLYCD | 1 hits |
| 31 | NLRP12 | 1 hits |
| 32 | NOS2A | 1 hits |
| 33 | NOS3 | 1 hits |
| 34 | NOX5 | 1 hits |
| 35 | NR3C1 | 1 hits |
| 36 | PDIK1L | 1 hits |
| 37 | PHLDA3 | 1 hits |
| 38 | PHLPP | 1 hits |
| 39 | PI3 | 1 hits |
| 40 | PIK3CA | 1 hits |
| 41 | PIK3CG | 1 hits |
| 42 | PPA1 | 1 hits |
| 43 | PPP1CA | 1 hits |
| 44 | PPP1R3C | 1 hits |
| 45 | PPP2R2A | 1 hits |
| 46 | PPP2R5B | 1 hits |
| 47 | PPP5C | 1 hits |
| 48 | PPYR1 | 1 hits |
| 49 | PRKAA1 | 1 hits |
| 50 | PRKAR2A | 1 hits |
| 51 | PTGES3 | 1 hits |
| 52 | PTGS2 | 1 hits |
| 53 | PTPN1 | 1 hits |
| 54 | PYGM | 1 hits |
| 55 | SASS6 | 1 hits |
| 56 | SET | 1 hits |
| 57 | SOD1 | 1 hits |
| 58 | SOD2 | 1 hits |
| 59 | TNF | 1 hits |
| 60 | YWHAQ | 1 hits |
Related Sentences
| # | PMID | Sentence |
| 1 | 1654859 | Protein phosphatase-1 and -2A, kinase FA, and casein kinase II in skeletal muscle of streptozotocin diabetic rats. |
| 2 | 1654859 | Protein phosphatase-1 (PP-1) and -2A (PP-2A), two regulatory subunits of PP-1, the glycogen-binding subunit G and inhibitor-2 (I-2), kinase FA, and casein kinase II (CK-II) were investigated in skeletal muscle of diabetic rats 2 days after streptozotocin injection. |
| 3 | 1654859 | FA and CK-II activate PP-1 in vitro and might be involved in the activation of PP-1 by insulin. |
| 4 | 1654859 | Following muscle fractionation we found that (1) diabetes decreased both basal and trypsin-stimulated PP-1 activities; the decrease was more significant in the glycogen-bound and microsomal fractions than in the cytosol (cytosolic PP-1 decreased as specific activity but not as activity/g of muscle); also PP-2A was lower in diabetic cytosols; (2) less G was immunoprecipitated from diabetic glycogen-bound fractions compared to controls, while I-2 was not significantly changed; (3) diabetes decreased also FA (assayed as PP-1 activator) and CK-II (assayed using a synthetic peptide as substrate); (4) diabetes did not have any effect on phosphorylase (a + b) activity in the glycogen-bound fraction. |
| 5 | 1654859 | Altogether the data show that acute diabetes decreased PP-1, one of its regulatory subunits and two potentially physiological regulators of PP-1, in addition to PP-2A. |
| 6 | 1654859 | Protein phosphatase-1 and -2A, kinase FA, and casein kinase II in skeletal muscle of streptozotocin diabetic rats. |
| 7 | 1654859 | Protein phosphatase-1 (PP-1) and -2A (PP-2A), two regulatory subunits of PP-1, the glycogen-binding subunit G and inhibitor-2 (I-2), kinase FA, and casein kinase II (CK-II) were investigated in skeletal muscle of diabetic rats 2 days after streptozotocin injection. |
| 8 | 1654859 | FA and CK-II activate PP-1 in vitro and might be involved in the activation of PP-1 by insulin. |
| 9 | 1654859 | Following muscle fractionation we found that (1) diabetes decreased both basal and trypsin-stimulated PP-1 activities; the decrease was more significant in the glycogen-bound and microsomal fractions than in the cytosol (cytosolic PP-1 decreased as specific activity but not as activity/g of muscle); also PP-2A was lower in diabetic cytosols; (2) less G was immunoprecipitated from diabetic glycogen-bound fractions compared to controls, while I-2 was not significantly changed; (3) diabetes decreased also FA (assayed as PP-1 activator) and CK-II (assayed using a synthetic peptide as substrate); (4) diabetes did not have any effect on phosphorylase (a + b) activity in the glycogen-bound fraction. |
| 10 | 1654859 | Altogether the data show that acute diabetes decreased PP-1, one of its regulatory subunits and two potentially physiological regulators of PP-1, in addition to PP-2A. |
| 11 | 1654859 | Protein phosphatase-1 and -2A, kinase FA, and casein kinase II in skeletal muscle of streptozotocin diabetic rats. |
| 12 | 1654859 | Protein phosphatase-1 (PP-1) and -2A (PP-2A), two regulatory subunits of PP-1, the glycogen-binding subunit G and inhibitor-2 (I-2), kinase FA, and casein kinase II (CK-II) were investigated in skeletal muscle of diabetic rats 2 days after streptozotocin injection. |
| 13 | 1654859 | FA and CK-II activate PP-1 in vitro and might be involved in the activation of PP-1 by insulin. |
| 14 | 1654859 | Following muscle fractionation we found that (1) diabetes decreased both basal and trypsin-stimulated PP-1 activities; the decrease was more significant in the glycogen-bound and microsomal fractions than in the cytosol (cytosolic PP-1 decreased as specific activity but not as activity/g of muscle); also PP-2A was lower in diabetic cytosols; (2) less G was immunoprecipitated from diabetic glycogen-bound fractions compared to controls, while I-2 was not significantly changed; (3) diabetes decreased also FA (assayed as PP-1 activator) and CK-II (assayed using a synthetic peptide as substrate); (4) diabetes did not have any effect on phosphorylase (a + b) activity in the glycogen-bound fraction. |
| 15 | 1654859 | Altogether the data show that acute diabetes decreased PP-1, one of its regulatory subunits and two potentially physiological regulators of PP-1, in addition to PP-2A. |
| 16 | 3034694 | Increase in liver protein phosphatase-1 in spontaneously diabetic Chinese hamsters. |
| 17 | 3034694 | Two broad-specifically protein phosphatases, termed protein phosphatase-1 (PrP-1) and protein phosphatase-2A (PrP-2A), accounting for all the hepatic activity regulating glycogen phosphorylase, were measured in spontaneously diabetic Chinese hamsters exhibiting persistent glycosuria. |
| 18 | 6327437 | Protein phosphatase-1 and -2A activities in heart, liver, and skeletal muscle extracts from control and diabetic rats. |
| 19 | 6327437 | The specific activity of protein phosphatase-1 in extracts of heart, liver, and skeletal muscle from control rats ranged between 0.34 and 0.44 U/mg protein. |
| 20 | 6327437 | The specific activity of a type 2 enzyme, termed protein phosphatase-2A, was approximately the same as protein phosphatase-1 in the case of skeletal muscle extracts, but was about 50% higher than type 1 in extracts from liver and heart. |
| 21 | 6327437 | The only significant effect of diabetes was on hepatic protein phosphatase-1 in which a 50% decrease in specific activity was noted. |
| 22 | 6327437 | Therefore, the effect of diabetes appeared to be confined to protein phosphatase-1 and this effect was only seen in liver. |
| 23 | 7487920 | Two compounds, (naphth-2-yl) difluoromethylphosphonic acid (12) and (napthy-1-yl) difluoromethylphosphonic acid (13) have been found to inhibit dephosphorylation of [32P]insulin receptors by PTP-1B, a protein tyrosine phosphatase (PTPase), with IC50 values of 40-50 microM. |
| 24 | 7487920 | Compound 12 competitively inhibited insulin-receptor dephosphorylation by PTP-1B. |
| 25 | 7487920 | Nine out of the 15 compounds potently inhibited serine/threonine phosphatase PP-2A activity without any effect on serine/threonine phosphatase PP-1 when tested at a concentration as high as 675 microM. |
| 26 | 7487920 | These PP-2A inhibitors could be useful tools for studying serine/threonine-phosphatase-mediated signal transduction. |
| 27 | 7487920 | Two compounds, 12 and 13, inhibited both tyrosine phosphatase PTP-1B and serine/threonine phosphatase PP-2A with similar potency; IC50 values being 40-50 microM in both cases. |
| 28 | 7487920 | Two compounds, (naphth-2-yl) difluoromethylphosphonic acid (12) and (napthy-1-yl) difluoromethylphosphonic acid (13) have been found to inhibit dephosphorylation of [32P]insulin receptors by PTP-1B, a protein tyrosine phosphatase (PTPase), with IC50 values of 40-50 microM. |
| 29 | 7487920 | Compound 12 competitively inhibited insulin-receptor dephosphorylation by PTP-1B. |
| 30 | 7487920 | Nine out of the 15 compounds potently inhibited serine/threonine phosphatase PP-2A activity without any effect on serine/threonine phosphatase PP-1 when tested at a concentration as high as 675 microM. |
| 31 | 7487920 | These PP-2A inhibitors could be useful tools for studying serine/threonine-phosphatase-mediated signal transduction. |
| 32 | 7487920 | Two compounds, 12 and 13, inhibited both tyrosine phosphatase PTP-1B and serine/threonine phosphatase PP-2A with similar potency; IC50 values being 40-50 microM in both cases. |
| 33 | 7487920 | Two compounds, (naphth-2-yl) difluoromethylphosphonic acid (12) and (napthy-1-yl) difluoromethylphosphonic acid (13) have been found to inhibit dephosphorylation of [32P]insulin receptors by PTP-1B, a protein tyrosine phosphatase (PTPase), with IC50 values of 40-50 microM. |
| 34 | 7487920 | Compound 12 competitively inhibited insulin-receptor dephosphorylation by PTP-1B. |
| 35 | 7487920 | Nine out of the 15 compounds potently inhibited serine/threonine phosphatase PP-2A activity without any effect on serine/threonine phosphatase PP-1 when tested at a concentration as high as 675 microM. |
| 36 | 7487920 | These PP-2A inhibitors could be useful tools for studying serine/threonine-phosphatase-mediated signal transduction. |
| 37 | 7487920 | Two compounds, 12 and 13, inhibited both tyrosine phosphatase PTP-1B and serine/threonine phosphatase PP-2A with similar potency; IC50 values being 40-50 microM in both cases. |
| 38 | 7683695 | Glucocorticoid regulation of insulin receptor and substrate IRS-1 tyrosine phosphorylation in rat skeletal muscle in vivo. |
| 39 | 7683695 | To test the hypothesis that glucocorticoid-induced insulin resistance might originate from abnormalities in insulin receptor signaling, we investigated the effects of glucocorticoids on in vivo tyrosine phosphorylation of the insulin receptor and the insulin receptor substrate IRS-1 in rat skeletal muscle. |
| 40 | 7683695 | Insulin receptors and substrate IRS-1 were identified and quantified with specific antibodies. |
| 41 | 7683695 | Treatment with protein phosphatase-2A reduced IRS-1 M(r) in control but not in glucocorticoid-treated muscle indicating that the lower M(r) likely results from lower phosphoserine and/or phosphothreonine content. |
| 42 | 7683695 | Subsequent treatment with cortisone for 5 d had no effects on insulin levels, tyrosine phosphorylation of insulin receptors or IRS-1, or the M(r) of IRS-1. |
| 43 | 7683695 | In conclusion, glucocorticoid-treated skeletal muscle is characterized by: (a) decreased total tyrosine phosphorylation of insulin receptors as a result of a reduction in the pool of receptors undergoing tyrosine phosphorylation; (b) decreased IRS-1 content and reduced serine and/or threonine phosphorylation of IRS-1. |
| 44 | 7822300 | Stimulation of protein phosphatase-1 activity by insulin in rat adipocytes. |
| 45 | 7822300 | In this study, we examined the distribution of protein serine/threonine phosphatase-1 (PP-1) and analyzed the effect of insulin on PP-1 and its mechanism of activation in freshly isolated rat adipocytes. |
| 46 | 7822300 | The adipocyte particulate fraction (PF) constituted approximately 80% of cellular PP-1 activity, while PP-2A was entirely cytosolic. |
| 47 | 7822300 | Insulin rapidly stimulated PF PP-1 in a time- and dose-dependent manner (maximum stimulation at 5 min with 4 nM insulin). |
| 48 | 7822300 | Immunoprecipitation of PF with an antibody against the site-1 sequence of rabbit skeletal muscle glycogen-associated PP-1 (PP-1G) subunit indicated that approximately 40% of adipocyte PP-1 activity was due to PP-1G form of the enzyme. |
| 49 | 7822300 | Insulin stimulated PP-1G (120% over basal levels) without affecting the other forms of PP-1 in the PF. |
| 50 | 7822300 | Insulin activation of PP-1 was accompanied by > 2-fold increase in the phosphorylation state of the 160-kDa regulatory subunit of PP-1. |
| 51 | 7822300 | Stimulation of p21Ras/mitogen-activated protein kinase pathway (MAP) with GTP analogues also resulted in stimulation of PP-1 similar to insulin. |
| 52 | 7822300 | The insulin effect on MAP kinase and PP-1 activation was blocked by a GTP antagonist, guanyl-5'-yl thiophosphate. |
| 53 | 7822300 | The inhibitors of MAP kinase activation (viz. cAMP agonists, SpcAMP and ML-9) also blocked PP-1 stimulation by insulin. |
| 54 | 7822300 | The time course of MAP kinase activation preceded the phosphorylation of PP-1 regulatory subunit and PP-1 activation. |
| 55 | 7822300 | We conclude that insulin rapidly activates a membrane-associated PP-1 in adipocytes, which may be similar to rabbit skeletal muscle PP-1G, and the activation is mediated by p21Ras/MAP kinase pathway. |
| 56 | 8083198 | A synthetic tris-sulfotyrosyl dodecapeptide (TRDIY(S)ETDY(S)Y(S)RK-amide), whose primary sequence is identical to the 1142-1153 sequence of the insulin proreceptor, inhibited insulin receptor dephosphorylation in solubilized membranes, and digitonin-permeabilized cells derived from Chinese hamster ovary (CHO) cells expressing high levels of human insulin receptors (CHO/HIRc). |
| 57 | 8083198 | The peptide displayed specificity toward tyrosine-class phosphatases only, as it had no effect on the activities of the serine/threonine phosphatases PP-1 and PP-2A, or alkaline phosphatase. |
| 58 | 8175660 | Regulation of protein phosphatase 1 and 2A activities by insulin during myogenesis in rat skeletal muscle cells in culture. |
| 59 | 8175660 | In this study, we examined protein phosphatase 1 (PP-1) and protein phosphatase 2A (PP-2A) activities during various stages of myogenesis and their regulation by insulin in rat skeletal muscle cells. |
| 60 | 8175660 | Spontaneous PP-1 activity increased progressively in cultures from 2 to 5 days, PP-2A activities remained constant in days 2-4 cultures and increased sharply on day 5. |
| 61 | 8175660 | Insulin stimulated PP-1 activity (40-80% increase over basal) in a time (t1/2 approximately 5 min)- and dose (EC50 approximately 0.1 nM)-dependent manner. |
| 62 | 8175660 | Insulin activation of PP-1 was accompanied by a corresponding inhibition in PP-2A activity. |
| 63 | 8175660 | The effects of insulin on PP-1 and PP-2A were differentiation dependent and were observed only in cells at fusion (day 5) and post-fusion. |
| 64 | 8175660 | The insulin's effect on PP-1 correlated with the gradual appearance of PP-1 G subunit in cells at fusion. |
| 65 | 8175660 | Immunoprecipitation of PP-1 from 32P-labeled cells with an antibody directed against the site 1 sequence of rabbit skeletal muscle PP-1G detected a 160-kDa protein, phosphorylation of which was significantly increased by insulin. |
| 66 | 8175660 | Treatment of cells with a cAMP agonist (SpcAMP) completely blocked activation of PP-1 by insulin and diminished insulin-stimulated phosphorylation of the 160-kDa protein. |
| 67 | 8175660 | From these studies, we conclude that insulin activates PP-1 in L6 cells by increasing the phosphorylation of its regulatory subunit. |
| 68 | 8175660 | Regulation of protein phosphatase 1 and 2A activities by insulin during myogenesis in rat skeletal muscle cells in culture. |
| 69 | 8175660 | In this study, we examined protein phosphatase 1 (PP-1) and protein phosphatase 2A (PP-2A) activities during various stages of myogenesis and their regulation by insulin in rat skeletal muscle cells. |
| 70 | 8175660 | Spontaneous PP-1 activity increased progressively in cultures from 2 to 5 days, PP-2A activities remained constant in days 2-4 cultures and increased sharply on day 5. |
| 71 | 8175660 | Insulin stimulated PP-1 activity (40-80% increase over basal) in a time (t1/2 approximately 5 min)- and dose (EC50 approximately 0.1 nM)-dependent manner. |
| 72 | 8175660 | Insulin activation of PP-1 was accompanied by a corresponding inhibition in PP-2A activity. |
| 73 | 8175660 | The effects of insulin on PP-1 and PP-2A were differentiation dependent and were observed only in cells at fusion (day 5) and post-fusion. |
| 74 | 8175660 | The insulin's effect on PP-1 correlated with the gradual appearance of PP-1 G subunit in cells at fusion. |
| 75 | 8175660 | Immunoprecipitation of PP-1 from 32P-labeled cells with an antibody directed against the site 1 sequence of rabbit skeletal muscle PP-1G detected a 160-kDa protein, phosphorylation of which was significantly increased by insulin. |
| 76 | 8175660 | Treatment of cells with a cAMP agonist (SpcAMP) completely blocked activation of PP-1 by insulin and diminished insulin-stimulated phosphorylation of the 160-kDa protein. |
| 77 | 8175660 | From these studies, we conclude that insulin activates PP-1 in L6 cells by increasing the phosphorylation of its regulatory subunit. |
| 78 | 8175660 | Regulation of protein phosphatase 1 and 2A activities by insulin during myogenesis in rat skeletal muscle cells in culture. |
| 79 | 8175660 | In this study, we examined protein phosphatase 1 (PP-1) and protein phosphatase 2A (PP-2A) activities during various stages of myogenesis and their regulation by insulin in rat skeletal muscle cells. |
| 80 | 8175660 | Spontaneous PP-1 activity increased progressively in cultures from 2 to 5 days, PP-2A activities remained constant in days 2-4 cultures and increased sharply on day 5. |
| 81 | 8175660 | Insulin stimulated PP-1 activity (40-80% increase over basal) in a time (t1/2 approximately 5 min)- and dose (EC50 approximately 0.1 nM)-dependent manner. |
| 82 | 8175660 | Insulin activation of PP-1 was accompanied by a corresponding inhibition in PP-2A activity. |
| 83 | 8175660 | The effects of insulin on PP-1 and PP-2A were differentiation dependent and were observed only in cells at fusion (day 5) and post-fusion. |
| 84 | 8175660 | The insulin's effect on PP-1 correlated with the gradual appearance of PP-1 G subunit in cells at fusion. |
| 85 | 8175660 | Immunoprecipitation of PP-1 from 32P-labeled cells with an antibody directed against the site 1 sequence of rabbit skeletal muscle PP-1G detected a 160-kDa protein, phosphorylation of which was significantly increased by insulin. |
| 86 | 8175660 | Treatment of cells with a cAMP agonist (SpcAMP) completely blocked activation of PP-1 by insulin and diminished insulin-stimulated phosphorylation of the 160-kDa protein. |
| 87 | 8175660 | From these studies, we conclude that insulin activates PP-1 in L6 cells by increasing the phosphorylation of its regulatory subunit. |
| 88 | 8175660 | Regulation of protein phosphatase 1 and 2A activities by insulin during myogenesis in rat skeletal muscle cells in culture. |
| 89 | 8175660 | In this study, we examined protein phosphatase 1 (PP-1) and protein phosphatase 2A (PP-2A) activities during various stages of myogenesis and their regulation by insulin in rat skeletal muscle cells. |
| 90 | 8175660 | Spontaneous PP-1 activity increased progressively in cultures from 2 to 5 days, PP-2A activities remained constant in days 2-4 cultures and increased sharply on day 5. |
| 91 | 8175660 | Insulin stimulated PP-1 activity (40-80% increase over basal) in a time (t1/2 approximately 5 min)- and dose (EC50 approximately 0.1 nM)-dependent manner. |
| 92 | 8175660 | Insulin activation of PP-1 was accompanied by a corresponding inhibition in PP-2A activity. |
| 93 | 8175660 | The effects of insulin on PP-1 and PP-2A were differentiation dependent and were observed only in cells at fusion (day 5) and post-fusion. |
| 94 | 8175660 | The insulin's effect on PP-1 correlated with the gradual appearance of PP-1 G subunit in cells at fusion. |
| 95 | 8175660 | Immunoprecipitation of PP-1 from 32P-labeled cells with an antibody directed against the site 1 sequence of rabbit skeletal muscle PP-1G detected a 160-kDa protein, phosphorylation of which was significantly increased by insulin. |
| 96 | 8175660 | Treatment of cells with a cAMP agonist (SpcAMP) completely blocked activation of PP-1 by insulin and diminished insulin-stimulated phosphorylation of the 160-kDa protein. |
| 97 | 8175660 | From these studies, we conclude that insulin activates PP-1 in L6 cells by increasing the phosphorylation of its regulatory subunit. |
| 98 | 8404657 | Protein phosphatase-1 and -2a activities in cultured fetal chick neurons: differential regulation by insulin and insulin-like growth factor-I. |
| 99 | 8404657 | In this study, we examined the developmental expression and regulation by insulin and insulin-like growth factor-I (IGF-I) of protein phosphatase-1 (PP-1) and protein phosphatase-2A (PP-2A) in cultured fetal chick neurons. |
| 100 | 8404657 | Insulin stimulated neuronal PP-1 activity in day 4 and 5 cultures, but had no effect in earlier cultures. |
| 101 | 8404657 | The activation of PP-1 by insulin was rapid, with a maximal effect (30-40% increase over basal levels) at 5 min with 10 ng/ml insulin. |
| 102 | 8404657 | Insulin did not alter total (trypsin-released) PP-1 activity, the content of PP-1 catalytic subunit, or PP-2A activity at any time in culture. |
| 103 | 8404657 | In contrast to insulin, IGF-I had no effect on PP-1 activity at any time in culture, but significantly increased PP-2A activity in day 5 cultures. |
| 104 | 8404657 | Maximal stimulation of PP-2A activity by IGF-I was observed at 10 min, with an EC50 of 5 ng/ml. |
| 105 | 8404657 | These results indicate that chick forebrain neurons contain both PP-1 and PP-2A activities and that neuronal PP-1 and PP-2A activities are differentially regulated by insulin and IGF-I. |
| 106 | 8404657 | We conclude that although insulin and IGF-I share many steps in signal transduction, these growth factors have distinct actions on neuronal phosphatase activity that may impact on differences in their neurotropic actions. |
| 107 | 8404657 | Protein phosphatase-1 and -2a activities in cultured fetal chick neurons: differential regulation by insulin and insulin-like growth factor-I. |
| 108 | 8404657 | In this study, we examined the developmental expression and regulation by insulin and insulin-like growth factor-I (IGF-I) of protein phosphatase-1 (PP-1) and protein phosphatase-2A (PP-2A) in cultured fetal chick neurons. |
| 109 | 8404657 | Insulin stimulated neuronal PP-1 activity in day 4 and 5 cultures, but had no effect in earlier cultures. |
| 110 | 8404657 | The activation of PP-1 by insulin was rapid, with a maximal effect (30-40% increase over basal levels) at 5 min with 10 ng/ml insulin. |
| 111 | 8404657 | Insulin did not alter total (trypsin-released) PP-1 activity, the content of PP-1 catalytic subunit, or PP-2A activity at any time in culture. |
| 112 | 8404657 | In contrast to insulin, IGF-I had no effect on PP-1 activity at any time in culture, but significantly increased PP-2A activity in day 5 cultures. |
| 113 | 8404657 | Maximal stimulation of PP-2A activity by IGF-I was observed at 10 min, with an EC50 of 5 ng/ml. |
| 114 | 8404657 | These results indicate that chick forebrain neurons contain both PP-1 and PP-2A activities and that neuronal PP-1 and PP-2A activities are differentially regulated by insulin and IGF-I. |
| 115 | 8404657 | We conclude that although insulin and IGF-I share many steps in signal transduction, these growth factors have distinct actions on neuronal phosphatase activity that may impact on differences in their neurotropic actions. |
| 116 | 8404657 | Protein phosphatase-1 and -2a activities in cultured fetal chick neurons: differential regulation by insulin and insulin-like growth factor-I. |
| 117 | 8404657 | In this study, we examined the developmental expression and regulation by insulin and insulin-like growth factor-I (IGF-I) of protein phosphatase-1 (PP-1) and protein phosphatase-2A (PP-2A) in cultured fetal chick neurons. |
| 118 | 8404657 | Insulin stimulated neuronal PP-1 activity in day 4 and 5 cultures, but had no effect in earlier cultures. |
| 119 | 8404657 | The activation of PP-1 by insulin was rapid, with a maximal effect (30-40% increase over basal levels) at 5 min with 10 ng/ml insulin. |
| 120 | 8404657 | Insulin did not alter total (trypsin-released) PP-1 activity, the content of PP-1 catalytic subunit, or PP-2A activity at any time in culture. |
| 121 | 8404657 | In contrast to insulin, IGF-I had no effect on PP-1 activity at any time in culture, but significantly increased PP-2A activity in day 5 cultures. |
| 122 | 8404657 | Maximal stimulation of PP-2A activity by IGF-I was observed at 10 min, with an EC50 of 5 ng/ml. |
| 123 | 8404657 | These results indicate that chick forebrain neurons contain both PP-1 and PP-2A activities and that neuronal PP-1 and PP-2A activities are differentially regulated by insulin and IGF-I. |
| 124 | 8404657 | We conclude that although insulin and IGF-I share many steps in signal transduction, these growth factors have distinct actions on neuronal phosphatase activity that may impact on differences in their neurotropic actions. |
| 125 | 8404657 | Protein phosphatase-1 and -2a activities in cultured fetal chick neurons: differential regulation by insulin and insulin-like growth factor-I. |
| 126 | 8404657 | In this study, we examined the developmental expression and regulation by insulin and insulin-like growth factor-I (IGF-I) of protein phosphatase-1 (PP-1) and protein phosphatase-2A (PP-2A) in cultured fetal chick neurons. |
| 127 | 8404657 | Insulin stimulated neuronal PP-1 activity in day 4 and 5 cultures, but had no effect in earlier cultures. |
| 128 | 8404657 | The activation of PP-1 by insulin was rapid, with a maximal effect (30-40% increase over basal levels) at 5 min with 10 ng/ml insulin. |
| 129 | 8404657 | Insulin did not alter total (trypsin-released) PP-1 activity, the content of PP-1 catalytic subunit, or PP-2A activity at any time in culture. |
| 130 | 8404657 | In contrast to insulin, IGF-I had no effect on PP-1 activity at any time in culture, but significantly increased PP-2A activity in day 5 cultures. |
| 131 | 8404657 | Maximal stimulation of PP-2A activity by IGF-I was observed at 10 min, with an EC50 of 5 ng/ml. |
| 132 | 8404657 | These results indicate that chick forebrain neurons contain both PP-1 and PP-2A activities and that neuronal PP-1 and PP-2A activities are differentially regulated by insulin and IGF-I. |
| 133 | 8404657 | We conclude that although insulin and IGF-I share many steps in signal transduction, these growth factors have distinct actions on neuronal phosphatase activity that may impact on differences in their neurotropic actions. |
| 134 | 8404657 | Protein phosphatase-1 and -2a activities in cultured fetal chick neurons: differential regulation by insulin and insulin-like growth factor-I. |
| 135 | 8404657 | In this study, we examined the developmental expression and regulation by insulin and insulin-like growth factor-I (IGF-I) of protein phosphatase-1 (PP-1) and protein phosphatase-2A (PP-2A) in cultured fetal chick neurons. |
| 136 | 8404657 | Insulin stimulated neuronal PP-1 activity in day 4 and 5 cultures, but had no effect in earlier cultures. |
| 137 | 8404657 | The activation of PP-1 by insulin was rapid, with a maximal effect (30-40% increase over basal levels) at 5 min with 10 ng/ml insulin. |
| 138 | 8404657 | Insulin did not alter total (trypsin-released) PP-1 activity, the content of PP-1 catalytic subunit, or PP-2A activity at any time in culture. |
| 139 | 8404657 | In contrast to insulin, IGF-I had no effect on PP-1 activity at any time in culture, but significantly increased PP-2A activity in day 5 cultures. |
| 140 | 8404657 | Maximal stimulation of PP-2A activity by IGF-I was observed at 10 min, with an EC50 of 5 ng/ml. |
| 141 | 8404657 | These results indicate that chick forebrain neurons contain both PP-1 and PP-2A activities and that neuronal PP-1 and PP-2A activities are differentially regulated by insulin and IGF-I. |
| 142 | 8404657 | We conclude that although insulin and IGF-I share many steps in signal transduction, these growth factors have distinct actions on neuronal phosphatase activity that may impact on differences in their neurotropic actions. |
| 143 | 8641197 | Effect of tumor necrosis factor-alpha on insulin action in cultured rat skeletal muscle cells. |
| 144 | 8641197 | In this study, the acute effects of tumor necrosis factor (TNF)-alpha on insulin-stimulated glucose uptake, glycogen synthesis, and protein phosphatase-1 (PP-1) activation were examined in cultured rat skeletal muscle cell line, L6. |
| 145 | 8641197 | Exposure of L6 cells to low concentrations of TNF-alpha (10 ng/ml for 60 min) inhibited basal and insulin stimulated 2-deoxyglucose uptake (40-50% decrease in basal and insulin stimulated glucose uptake respectively, when compared with controls, P < 0.05). |
| 146 | 8641197 | TNF-alpha also blocked insulin activation of glycogen synthase (GS) and inhibited glycogen synthesis (measured as [14C]-glucose incorporated into glycogen). |
| 147 | 8641197 | Because GS is activated by dephosphorylation via protein phosphatase-1 (PP-1), we examined the effect of TNF- alpha on PP-1 activation. |
| 148 | 8641197 | Begum, J Biol Chem 269:16662-16667, 1994), insulin rapidly stimulated PP-1 and concomitantly inhibited PP-2A activities in L6 cells. |
| 149 | 8641197 | Pretreatment with TNF- alpha for 10-60 min blocked subsequent insulin-induced activation of PP-1. |
| 150 | 8641197 | The impaired activation of PP-1 was accompanied by a reduction in insulin-stimulated phosphorylation of the regulatory subunit of PP-1. cAMP-Rp diastereomer, a cAMP antagonist failed to prevent the detrimental effects of TNF-alpha on PP-1. |
| 151 | 8641197 | Cell permeable ceramide analogs, C2, C6, and Sphingomyelinase mimicked the effects of TNF-alpha on PP-1 inhibition. |
| 152 | 8641197 | We conclude that TNF-alpha blocks insulin-stimulated glycogen synthesis by inhibiting PP-1 activation via ceramide release. |
| 153 | 8665940 | Effect of tumor necrosis factor-alpha on insulin-stimulated mitogen-activated protein kinase cascade in cultured rat skeletal muscle cells. |
| 154 | 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. |
| 155 | 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. |
| 156 | 8665940 | Insulin treatment of L6 cells resulted in a rapid increase in MAPK activity (> twofold in 5 min with 10 nM insulin). |
| 157 | 8665940 | Prior treatment with TNF-alpha for 60 min blocked subsequent insulin-induced activation of MAPK in a dose- and time-dependent manner. |
| 158 | 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. |
| 159 | 8665940 | This effect of TNF-alpha was not due to inhibition of insulin-stimulated p21ras-GTP loading or Raf-1 phosphorylation. |
| 160 | 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. |
| 161 | 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. |
| 162 | 8665940 | Therefore, we examined the effect of TNF-alpha on protein phosphatase-1 (PP-1) and protein phosphatase-2A (PP-2A) activities. |
| 163 | 8665940 | As reported by us earlier, insulin rapidly stimulated PP-1 and concomitantly inhibited PP-2A activities in control cells. |
| 164 | 8665940 | TNF-alpha treatment blocked insulin-induced activation of PP-1. |
| 165 | 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. |
| 166 | 8665940 | The time course of PP-2A activation by TNF-alpha preceded the kinetics of inhibition of MAPK. |
| 167 | 8665940 | Cell-permeable ceramide analogs mimicked the TNF-alpha effect on MAPK inhibition and PP-2A activation. |
| 168 | 8665940 | We conclude that TNF-alpha abrogates the insulin effect on MAPK activation by increasing dephosphorylation of MAPK kinase via an activated phosphatase. |
| 169 | 8665940 | Effect of tumor necrosis factor-alpha on insulin-stimulated mitogen-activated protein kinase cascade in cultured rat skeletal muscle cells. |
| 170 | 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. |
| 171 | 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. |
| 172 | 8665940 | Insulin treatment of L6 cells resulted in a rapid increase in MAPK activity (> twofold in 5 min with 10 nM insulin). |
| 173 | 8665940 | Prior treatment with TNF-alpha for 60 min blocked subsequent insulin-induced activation of MAPK in a dose- and time-dependent manner. |
| 174 | 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. |
| 175 | 8665940 | This effect of TNF-alpha was not due to inhibition of insulin-stimulated p21ras-GTP loading or Raf-1 phosphorylation. |
| 176 | 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. |
| 177 | 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. |
| 178 | 8665940 | Therefore, we examined the effect of TNF-alpha on protein phosphatase-1 (PP-1) and protein phosphatase-2A (PP-2A) activities. |
| 179 | 8665940 | As reported by us earlier, insulin rapidly stimulated PP-1 and concomitantly inhibited PP-2A activities in control cells. |
| 180 | 8665940 | TNF-alpha treatment blocked insulin-induced activation of PP-1. |
| 181 | 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. |
| 182 | 8665940 | The time course of PP-2A activation by TNF-alpha preceded the kinetics of inhibition of MAPK. |
| 183 | 8665940 | Cell-permeable ceramide analogs mimicked the TNF-alpha effect on MAPK inhibition and PP-2A activation. |
| 184 | 8665940 | We conclude that TNF-alpha abrogates the insulin effect on MAPK activation by increasing dephosphorylation of MAPK kinase via an activated phosphatase. |
| 185 | 8665940 | Effect of tumor necrosis factor-alpha on insulin-stimulated mitogen-activated protein kinase cascade in cultured rat skeletal muscle cells. |
| 186 | 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. |
| 187 | 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. |
| 188 | 8665940 | Insulin treatment of L6 cells resulted in a rapid increase in MAPK activity (> twofold in 5 min with 10 nM insulin). |
| 189 | 8665940 | Prior treatment with TNF-alpha for 60 min blocked subsequent insulin-induced activation of MAPK in a dose- and time-dependent manner. |
| 190 | 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. |
| 191 | 8665940 | This effect of TNF-alpha was not due to inhibition of insulin-stimulated p21ras-GTP loading or Raf-1 phosphorylation. |
| 192 | 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. |
| 193 | 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. |
| 194 | 8665940 | Therefore, we examined the effect of TNF-alpha on protein phosphatase-1 (PP-1) and protein phosphatase-2A (PP-2A) activities. |
| 195 | 8665940 | As reported by us earlier, insulin rapidly stimulated PP-1 and concomitantly inhibited PP-2A activities in control cells. |
| 196 | 8665940 | TNF-alpha treatment blocked insulin-induced activation of PP-1. |
| 197 | 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. |
| 198 | 8665940 | The time course of PP-2A activation by TNF-alpha preceded the kinetics of inhibition of MAPK. |
| 199 | 8665940 | Cell-permeable ceramide analogs mimicked the TNF-alpha effect on MAPK inhibition and PP-2A activation. |
| 200 | 8665940 | We conclude that TNF-alpha abrogates the insulin effect on MAPK activation by increasing dephosphorylation of MAPK kinase via an activated phosphatase. |
| 201 | 8665940 | Effect of tumor necrosis factor-alpha on insulin-stimulated mitogen-activated protein kinase cascade in cultured rat skeletal muscle cells. |
| 202 | 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. |
| 203 | 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. |
| 204 | 8665940 | Insulin treatment of L6 cells resulted in a rapid increase in MAPK activity (> twofold in 5 min with 10 nM insulin). |
| 205 | 8665940 | Prior treatment with TNF-alpha for 60 min blocked subsequent insulin-induced activation of MAPK in a dose- and time-dependent manner. |
| 206 | 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. |
| 207 | 8665940 | This effect of TNF-alpha was not due to inhibition of insulin-stimulated p21ras-GTP loading or Raf-1 phosphorylation. |
| 208 | 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. |
| 209 | 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. |
| 210 | 8665940 | Therefore, we examined the effect of TNF-alpha on protein phosphatase-1 (PP-1) and protein phosphatase-2A (PP-2A) activities. |
| 211 | 8665940 | As reported by us earlier, insulin rapidly stimulated PP-1 and concomitantly inhibited PP-2A activities in control cells. |
| 212 | 8665940 | TNF-alpha treatment blocked insulin-induced activation of PP-1. |
| 213 | 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. |
| 214 | 8665940 | The time course of PP-2A activation by TNF-alpha preceded the kinetics of inhibition of MAPK. |
| 215 | 8665940 | Cell-permeable ceramide analogs mimicked the TNF-alpha effect on MAPK inhibition and PP-2A activation. |
| 216 | 8665940 | We conclude that TNF-alpha abrogates the insulin effect on MAPK activation by increasing dephosphorylation of MAPK kinase via an activated phosphatase. |
| 217 | 8665940 | Effect of tumor necrosis factor-alpha on insulin-stimulated mitogen-activated protein kinase cascade in cultured rat skeletal muscle cells. |
| 218 | 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. |
| 219 | 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. |
| 220 | 8665940 | Insulin treatment of L6 cells resulted in a rapid increase in MAPK activity (> twofold in 5 min with 10 nM insulin). |
| 221 | 8665940 | Prior treatment with TNF-alpha for 60 min blocked subsequent insulin-induced activation of MAPK in a dose- and time-dependent manner. |
| 222 | 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. |
| 223 | 8665940 | This effect of TNF-alpha was not due to inhibition of insulin-stimulated p21ras-GTP loading or Raf-1 phosphorylation. |
| 224 | 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. |
| 225 | 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. |
| 226 | 8665940 | Therefore, we examined the effect of TNF-alpha on protein phosphatase-1 (PP-1) and protein phosphatase-2A (PP-2A) activities. |
| 227 | 8665940 | As reported by us earlier, insulin rapidly stimulated PP-1 and concomitantly inhibited PP-2A activities in control cells. |
| 228 | 8665940 | TNF-alpha treatment blocked insulin-induced activation of PP-1. |
| 229 | 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. |
| 230 | 8665940 | The time course of PP-2A activation by TNF-alpha preceded the kinetics of inhibition of MAPK. |
| 231 | 8665940 | Cell-permeable ceramide analogs mimicked the TNF-alpha effect on MAPK inhibition and PP-2A activation. |
| 232 | 8665940 | We conclude that TNF-alpha abrogates the insulin effect on MAPK activation by increasing dephosphorylation of MAPK kinase via an activated phosphatase. |
| 233 | 8832569 | Ventricular cardiomyocytes isolated from adult rat heart were used to analyze the effect of insulin on the phosphorylation of DNA-binding nuclear proteins and to elucidate the potential involvement of protein phosphatase-1 (PP-1) and PP-2A in this hormonal action. |
| 234 | 8832569 | Immunoprecipitation and Western blotting experiments revealed the presence of phosphorylated numatrin in the nuclear extract, however, insulin did not modify its phosphorylation state. |
| 235 | 8832569 | Using 32P-labelled phosphorylase as a substrate, we observed a significant inhibition of nuclear PP-1 activity to 38.5 +/- 7% (n = 3) of control after incubation of cardiomyocytes with insulin for 15 min. |
| 236 | 8832569 | It is suggested that inhibition of nuclear PP-1 and PP-2A represents a possible mechanism of insulin signalling to the nucleus of target cells. |
| 237 | 8832569 | Ventricular cardiomyocytes isolated from adult rat heart were used to analyze the effect of insulin on the phosphorylation of DNA-binding nuclear proteins and to elucidate the potential involvement of protein phosphatase-1 (PP-1) and PP-2A in this hormonal action. |
| 238 | 8832569 | Immunoprecipitation and Western blotting experiments revealed the presence of phosphorylated numatrin in the nuclear extract, however, insulin did not modify its phosphorylation state. |
| 239 | 8832569 | Using 32P-labelled phosphorylase as a substrate, we observed a significant inhibition of nuclear PP-1 activity to 38.5 +/- 7% (n = 3) of control after incubation of cardiomyocytes with insulin for 15 min. |
| 240 | 8832569 | It is suggested that inhibition of nuclear PP-1 and PP-2A represents a possible mechanism of insulin signalling to the nucleus of target cells. |
| 241 | 8940115 | cAMP counter-regulates insulin-mediated protein phosphatase-2A inactivation in rat skeletal muscle cells. |
| 242 | 8940115 | In this study, we examined the mechanism of recently reported inactivation of protein phosphatase-2A (PP-2A) by insulin (Srinivasan, M., and Begum, N. (1994) J. |
| 243 | 8940115 | Exposure of L6 myotubes to insulin resulted in a rapid inhibition of PP-2A that was accompanied by a 3-fold increase in the phosphotyrosine content of the immunoprecipitated PP-2A catalytic subunit. |
| 244 | 8940115 | Pretreatment with (Sp)-cAMP, a cAMP agonist, completely blocked insulin-mediated inhibition of PP-2A activity and decreased the tyrosine phosphorylation of PP-2A catalytic subunit to control levels. |
| 245 | 8940115 | Wortmannin, a phosphatidylinositol 3-kinase inhibitor, and rapamycin, an inhibitor of 70-kDa S6 kinase activation, prevented insulin-mediated inactivation of PP-2A, suggesting that these pathways may participate in insulin-mediated phosphorylation and inactivation of PP-2A. |
| 246 | 8940115 | These results show that insulin signaling results in a rapid inactivation of PP-2A by increased tyrosine phosphorylation and cAMP agonists counter-regulate insulin's effect on PP-2A by decreasing phosphorylation, presumably via an activated phosphatase. |
| 247 | 8940115 | cAMP counter-regulates insulin-mediated protein phosphatase-2A inactivation in rat skeletal muscle cells. |
| 248 | 8940115 | In this study, we examined the mechanism of recently reported inactivation of protein phosphatase-2A (PP-2A) by insulin (Srinivasan, M., and Begum, N. (1994) J. |
| 249 | 8940115 | Exposure of L6 myotubes to insulin resulted in a rapid inhibition of PP-2A that was accompanied by a 3-fold increase in the phosphotyrosine content of the immunoprecipitated PP-2A catalytic subunit. |
| 250 | 8940115 | Pretreatment with (Sp)-cAMP, a cAMP agonist, completely blocked insulin-mediated inhibition of PP-2A activity and decreased the tyrosine phosphorylation of PP-2A catalytic subunit to control levels. |
| 251 | 8940115 | Wortmannin, a phosphatidylinositol 3-kinase inhibitor, and rapamycin, an inhibitor of 70-kDa S6 kinase activation, prevented insulin-mediated inactivation of PP-2A, suggesting that these pathways may participate in insulin-mediated phosphorylation and inactivation of PP-2A. |
| 252 | 8940115 | These results show that insulin signaling results in a rapid inactivation of PP-2A by increased tyrosine phosphorylation and cAMP agonists counter-regulate insulin's effect on PP-2A by decreasing phosphorylation, presumably via an activated phosphatase. |
| 253 | 8940115 | cAMP counter-regulates insulin-mediated protein phosphatase-2A inactivation in rat skeletal muscle cells. |
| 254 | 8940115 | In this study, we examined the mechanism of recently reported inactivation of protein phosphatase-2A (PP-2A) by insulin (Srinivasan, M., and Begum, N. (1994) J. |
| 255 | 8940115 | Exposure of L6 myotubes to insulin resulted in a rapid inhibition of PP-2A that was accompanied by a 3-fold increase in the phosphotyrosine content of the immunoprecipitated PP-2A catalytic subunit. |
| 256 | 8940115 | Pretreatment with (Sp)-cAMP, a cAMP agonist, completely blocked insulin-mediated inhibition of PP-2A activity and decreased the tyrosine phosphorylation of PP-2A catalytic subunit to control levels. |
| 257 | 8940115 | Wortmannin, a phosphatidylinositol 3-kinase inhibitor, and rapamycin, an inhibitor of 70-kDa S6 kinase activation, prevented insulin-mediated inactivation of PP-2A, suggesting that these pathways may participate in insulin-mediated phosphorylation and inactivation of PP-2A. |
| 258 | 8940115 | These results show that insulin signaling results in a rapid inactivation of PP-2A by increased tyrosine phosphorylation and cAMP agonists counter-regulate insulin's effect on PP-2A by decreasing phosphorylation, presumably via an activated phosphatase. |
| 259 | 8940115 | cAMP counter-regulates insulin-mediated protein phosphatase-2A inactivation in rat skeletal muscle cells. |
| 260 | 8940115 | In this study, we examined the mechanism of recently reported inactivation of protein phosphatase-2A (PP-2A) by insulin (Srinivasan, M., and Begum, N. (1994) J. |
| 261 | 8940115 | Exposure of L6 myotubes to insulin resulted in a rapid inhibition of PP-2A that was accompanied by a 3-fold increase in the phosphotyrosine content of the immunoprecipitated PP-2A catalytic subunit. |
| 262 | 8940115 | Pretreatment with (Sp)-cAMP, a cAMP agonist, completely blocked insulin-mediated inhibition of PP-2A activity and decreased the tyrosine phosphorylation of PP-2A catalytic subunit to control levels. |
| 263 | 8940115 | Wortmannin, a phosphatidylinositol 3-kinase inhibitor, and rapamycin, an inhibitor of 70-kDa S6 kinase activation, prevented insulin-mediated inactivation of PP-2A, suggesting that these pathways may participate in insulin-mediated phosphorylation and inactivation of PP-2A. |
| 264 | 8940115 | These results show that insulin signaling results in a rapid inactivation of PP-2A by increased tyrosine phosphorylation and cAMP agonists counter-regulate insulin's effect on PP-2A by decreasing phosphorylation, presumably via an activated phosphatase. |
| 265 | 8940115 | cAMP counter-regulates insulin-mediated protein phosphatase-2A inactivation in rat skeletal muscle cells. |
| 266 | 8940115 | In this study, we examined the mechanism of recently reported inactivation of protein phosphatase-2A (PP-2A) by insulin (Srinivasan, M., and Begum, N. (1994) J. |
| 267 | 8940115 | Exposure of L6 myotubes to insulin resulted in a rapid inhibition of PP-2A that was accompanied by a 3-fold increase in the phosphotyrosine content of the immunoprecipitated PP-2A catalytic subunit. |
| 268 | 8940115 | Pretreatment with (Sp)-cAMP, a cAMP agonist, completely blocked insulin-mediated inhibition of PP-2A activity and decreased the tyrosine phosphorylation of PP-2A catalytic subunit to control levels. |
| 269 | 8940115 | Wortmannin, a phosphatidylinositol 3-kinase inhibitor, and rapamycin, an inhibitor of 70-kDa S6 kinase activation, prevented insulin-mediated inactivation of PP-2A, suggesting that these pathways may participate in insulin-mediated phosphorylation and inactivation of PP-2A. |
| 270 | 8940115 | These results show that insulin signaling results in a rapid inactivation of PP-2A by increased tyrosine phosphorylation and cAMP agonists counter-regulate insulin's effect on PP-2A by decreasing phosphorylation, presumably via an activated phosphatase. |
| 271 | 8940115 | cAMP counter-regulates insulin-mediated protein phosphatase-2A inactivation in rat skeletal muscle cells. |
| 272 | 8940115 | In this study, we examined the mechanism of recently reported inactivation of protein phosphatase-2A (PP-2A) by insulin (Srinivasan, M., and Begum, N. (1994) J. |
| 273 | 8940115 | Exposure of L6 myotubes to insulin resulted in a rapid inhibition of PP-2A that was accompanied by a 3-fold increase in the phosphotyrosine content of the immunoprecipitated PP-2A catalytic subunit. |
| 274 | 8940115 | Pretreatment with (Sp)-cAMP, a cAMP agonist, completely blocked insulin-mediated inhibition of PP-2A activity and decreased the tyrosine phosphorylation of PP-2A catalytic subunit to control levels. |
| 275 | 8940115 | Wortmannin, a phosphatidylinositol 3-kinase inhibitor, and rapamycin, an inhibitor of 70-kDa S6 kinase activation, prevented insulin-mediated inactivation of PP-2A, suggesting that these pathways may participate in insulin-mediated phosphorylation and inactivation of PP-2A. |
| 276 | 8940115 | These results show that insulin signaling results in a rapid inactivation of PP-2A by increased tyrosine phosphorylation and cAMP agonists counter-regulate insulin's effect on PP-2A by decreasing phosphorylation, presumably via an activated phosphatase. |
| 277 | 9148944 | After 5 min of contraction, ACC-beta activity was decreased by 90% despite an apparent increase in the cytosolic concentration of citrate, a positive regulator of ACC. |
| 278 | 9148944 | In addition, homogenization of the muscles in a buffer free of phosphatase inhibitors and containing the phosphatase activators glutamate and MgCl2 or treatment of immunoprecipitated ACC-beta with purified protein phosphatase 2A abolished the decreases in both ACC-beta activity and electrophoretic mobility caused by contraction. |
| 279 | 9148944 | The rapid decrease in ACC-beta activity after the onset of contractions (50% by 20 s) and its slow restoration to initial values during recovery (60-90 min) were paralleled temporally by reciprocal changes in the activity of the alpha2 but not the alpha1 isoform of 5'-AMP-activated protein kinase (AMPK). |
| 280 | 9148944 | These alterations in ACC and AMPK activity, by diminishing the concentration of malonyl-CoA, could be responsible for the increase in fatty acid oxidation observed in skeletal muscle during exercise. |
| 281 | 9169593 | Insulin regulation of mitogen-activated protein kinase kinase (MEK), mitogen-activated protein kinase and casein kinase in the cell nucleus: a possible role in the regulation of gene expression. |
| 282 | 9169593 | After insulin receptor activation, many cytoplasmic enzymes, including mitogen-activated protein (MAP) kinase, MAP kinase kinase (MEK) and casein kinase II (CKII) are activated, but exactly how insulin signalling progresses to the nucleus remains poorly understood. |
| 283 | 9169593 | In Chinese hamster ovary cells overexpressing human insulin receptors [CHO(Hirc)], MEK, CKII and the MAP kinases ERK I and ERK II can be detected by immunoblotting in the nucleus, as well as in the cytoplasm, in the unstimulated state. |
| 284 | 9169593 | Nuclear localization of MAP kinase is also observed in 3T3-F442A adipocytes, NIH-3T3 cells and Fao hepatoma cells, whereas MEK is found in the nucleus only in Fao and CHO cells. |
| 285 | 9169593 | Insulin treatment for 5-30 min induces a translocation of MEK from the cytoplasm to the nucleus, whereas the MAP kinases and CKII are not translocated into the nucleus in response to insulin during this period. |
| 286 | 9169593 | However, nuclear MAP kinase and CKII activities increase by 2-3-fold within 1-10 min after stimulation with insulin. |
| 287 | 9169593 | By using gel-shift assays, it has been shown that insulin also stimulates nuclear protein binding to an AP-1 site with kinetics similar to MEK translocation and MAP kinase and CKII activation. |
| 288 | 9169593 | Treatment of the extracts in vitro with protein phosphatase 2A or treatment of the intact cells with 5, 6-dichloro-1-beta-d-ribofuranosylbenzimidazole, a cell-permeable inhibitor of CKII, almost completely blocks the insulin-induced DNA-binding activity, whereas incubation of cells with a MEK inhibitor produces only a slight decrease. |
| 289 | 9169593 | The latter is true of CKII, which seems to regulate the binding of nuclear proteins to the AP-1 site, possibly by phosphorylation of AP-1 transcription factors. |
| 290 | 9295306 | In this study, we examined the potential role of serine/threonine protein phosphatase-1 (PP-1) and PP-2A in the mechanism of Na+/K+-ATPase activation by insulin in the rat skeletal muscle cell line L6. |
| 291 | 9295306 | Immunoprecipitation of the enzyme from 32P-labeled cells with an antibody directed against the alpha-1 subunit of the enzyme revealed a 60% decrease in 110-kDa protein phosphorylation in insulin-treated cells. |
| 292 | 9295306 | To further confirm the role of PP-1, we used L6 cell lines that overexpress the glycogen/SR-associated regulatory subunit of PP-1, PP-1G. |
| 293 | 9295306 | Overexpression of PP-1G resulted in a 3-fold increase in insulin-stimulated PP-1 catalytic activity. |
| 294 | 9295306 | Inhibition of phosphatidylinositol-3 kinase with wortmannin blocked insulin-stimulated PP-1 activation as well as the dephosphorylation and activation of Na+/K+-ATPase. |
| 295 | 9295306 | We conclude that insulin regulates the activity of Na+/K+-ATPase by promoting dephosphorylation of the alpha subunit via an insulin-stimulated PP-1 and that phosphatidylinositol-3 kinase-generated signals may mediate insulin activation of PP-1 and Na+/K+-ATPase. |
| 296 | 9343928 | We have synthesized a tris-sulfotyrosyl dodecapeptide (3S-peptide-I) that corresponds to the major autophosphorylation domain within the insulin receptor beta-subunit and showed that it potently inhibited insulin receptor dephosphorylation by protein tyrosine phosphatases (PTPases) in vitro. 3S-peptide-I also inhibited tyrosine dephosphorylation of a synthetic peptide by the recombinant PTPase PTP-1B, indicating that 3S-peptide-I interacts directly with PTPase, causing its inactivation. |
| 297 | 9343928 | The peptide had no effect on the activity of serine/threonine phosphatases, PP-1 and PP-2A, or alkaline phosphatase. |
| 298 | 9343928 | Furthermore, we found that the introduction of a N-stearyl derivative of 3S-peptide-I in CHO/HIRc cells caused a significant increase in insulin-stimulated phosphorylation of the insulin receptor. |
| 299 | 9343928 | In contrast, ligand-stimulated phosphorylation of epidermal growth factor (EGF) receptor in CHO cells overexpressing EGF receptors was not affected by the presence of N-stearyl-3S-peptide-I. |
| 300 | 9440478 | In adipocytes isolated from control rats, insulin (5 nmol/L) stimulated particulate serine/threonine protein phosphatase-1 (PP-1) activity (56% increase over the basal value after 5 minutes). |
| 301 | 9440478 | In contrast, adipocytes from diabetic GK rats exhibited a 32% decrease in basal (P < .05) and a 65% decrease in insulin-stimulated PP-1 activity compared with values in control Wistar rats. |
| 302 | 9440478 | Insulin treatment resulted in a 50% to 60% inhibition in PP-2A activity in control rats, but failed to inhibit PP-2A activity in diabetic GK rat adipocytes. |
| 303 | 9440478 | The defects in PP-1/PP-2A activation/inactivation were accompanied by inhibition of insulin's effect on mitogen-activated protein kinase (MAPK) activation. |
| 304 | 9440478 | In addition, insulin-stimulated tyrosine phosphorylation of insulin receptor (IR) substrate-1 (IRS-1) was decreased more than 90% compared with control values, while a twofold increase in basal IRS-1 phosphorylation status was observed in diabetic GK rats. |
| 305 | 9440478 | The abnormalities in IRS-1 phosphorylation were accompanied by a severe impairment of insulin-mediated targeting of the Grb2/Sos complex to the plasma membrane. |
| 306 | 9440478 | We conclude that (1) a rapid activation of PP-1 along with concomitant inhibition of cytosolic PP-2A may be important in the mechanism of insulin action in a normal cell, and (2) the resistance to insulin in terms of glucose uptake and glycogen synthesis observed in diabetic GK rats is partly due to defective regulation of PP-1, PP-2A, and MAPK caused by multiple defects in the upstream insulin signaling components (IRS-1/phosphatidylinositol-3-kinase [PI3-kinase] and Grb2/Sos) that participate in insulin-mediated activation of PP-1 and inactivation of PP-2A. |
| 307 | 9440478 | In adipocytes isolated from control rats, insulin (5 nmol/L) stimulated particulate serine/threonine protein phosphatase-1 (PP-1) activity (56% increase over the basal value after 5 minutes). |
| 308 | 9440478 | In contrast, adipocytes from diabetic GK rats exhibited a 32% decrease in basal (P < .05) and a 65% decrease in insulin-stimulated PP-1 activity compared with values in control Wistar rats. |
| 309 | 9440478 | Insulin treatment resulted in a 50% to 60% inhibition in PP-2A activity in control rats, but failed to inhibit PP-2A activity in diabetic GK rat adipocytes. |
| 310 | 9440478 | The defects in PP-1/PP-2A activation/inactivation were accompanied by inhibition of insulin's effect on mitogen-activated protein kinase (MAPK) activation. |
| 311 | 9440478 | In addition, insulin-stimulated tyrosine phosphorylation of insulin receptor (IR) substrate-1 (IRS-1) was decreased more than 90% compared with control values, while a twofold increase in basal IRS-1 phosphorylation status was observed in diabetic GK rats. |
| 312 | 9440478 | The abnormalities in IRS-1 phosphorylation were accompanied by a severe impairment of insulin-mediated targeting of the Grb2/Sos complex to the plasma membrane. |
| 313 | 9440478 | We conclude that (1) a rapid activation of PP-1 along with concomitant inhibition of cytosolic PP-2A may be important in the mechanism of insulin action in a normal cell, and (2) the resistance to insulin in terms of glucose uptake and glycogen synthesis observed in diabetic GK rats is partly due to defective regulation of PP-1, PP-2A, and MAPK caused by multiple defects in the upstream insulin signaling components (IRS-1/phosphatidylinositol-3-kinase [PI3-kinase] and Grb2/Sos) that participate in insulin-mediated activation of PP-1 and inactivation of PP-2A. |
| 314 | 9440478 | In adipocytes isolated from control rats, insulin (5 nmol/L) stimulated particulate serine/threonine protein phosphatase-1 (PP-1) activity (56% increase over the basal value after 5 minutes). |
| 315 | 9440478 | In contrast, adipocytes from diabetic GK rats exhibited a 32% decrease in basal (P < .05) and a 65% decrease in insulin-stimulated PP-1 activity compared with values in control Wistar rats. |
| 316 | 9440478 | Insulin treatment resulted in a 50% to 60% inhibition in PP-2A activity in control rats, but failed to inhibit PP-2A activity in diabetic GK rat adipocytes. |
| 317 | 9440478 | The defects in PP-1/PP-2A activation/inactivation were accompanied by inhibition of insulin's effect on mitogen-activated protein kinase (MAPK) activation. |
| 318 | 9440478 | In addition, insulin-stimulated tyrosine phosphorylation of insulin receptor (IR) substrate-1 (IRS-1) was decreased more than 90% compared with control values, while a twofold increase in basal IRS-1 phosphorylation status was observed in diabetic GK rats. |
| 319 | 9440478 | The abnormalities in IRS-1 phosphorylation were accompanied by a severe impairment of insulin-mediated targeting of the Grb2/Sos complex to the plasma membrane. |
| 320 | 9440478 | We conclude that (1) a rapid activation of PP-1 along with concomitant inhibition of cytosolic PP-2A may be important in the mechanism of insulin action in a normal cell, and (2) the resistance to insulin in terms of glucose uptake and glycogen synthesis observed in diabetic GK rats is partly due to defective regulation of PP-1, PP-2A, and MAPK caused by multiple defects in the upstream insulin signaling components (IRS-1/phosphatidylinositol-3-kinase [PI3-kinase] and Grb2/Sos) that participate in insulin-mediated activation of PP-1 and inactivation of PP-2A. |
| 321 | 9609113 | Protein phosphatase-1 and insulin action. |
| 322 | 9609113 | Protein Phosphatase-1 (PP-1) appears to be the key component of the insulin signalling pathway which is responsible for bridging the initial insulin-simulated phosphorylation cascade with the ultimate dephosphorylation of insulin sensitive substrates. |
| 323 | 9609113 | Dephosphorylations catalyzed by PP-1 activate glycogen synthase (GS) and simultaneously inactivate phosphorylase a and phosphorylase kinase promoting glycogen synthesis. |
| 324 | 9609113 | Our in vivo studies using L6 rat skeletal muscle cells and freshly isolated adipocytes indicate that insulin stimulates PP-1 by increasing the phosphorylation status of its regulatory subunit (PP-1G). |
| 325 | 9609113 | PP-1 activation is accompanied by an inactivation of Protein Phosphatase-2A (PP-2A) activity. |
| 326 | 9609113 | To gain insight into the upstream kinases that mediate insulin-stimulated PP-1G phosphorylation, we employed inhibitors of the ras/MAPK, PI3-kinase, and PKC signalling pathways. |
| 327 | 9609113 | These inhibitor studies suggest that PP-1G phosphorylation is mediated via a complex, cell type specific mechanism involving PI3-kinase/PKC/PKB and/or the ras/MAP kinase/Rsk kinase cascade. cAMP agonists such as SpcAMP (via PKA) and TNF-alpha (recently identified as endogenous inhibitor of insulin action via ceramide) block insulin-stimulated PP-1G phosphorylation with a parallel decrease of PP-1 activity, presumably due to the dissociation of the PP-1 catalytic subunit from the regulatory G-subunit. |
| 328 | 9609113 | It appears that any agent or condition which interferes with the insulin-induced phosphorylation and activation of PP-1, will decrease the magnitude of insulin's effect on downstream metabolic processes. |
| 329 | 9609113 | Therefore, regulation of the PP-1G subunit by site-specific phosphorylation plays an important role in insulin signal transduction in target cells. |
| 330 | 9609113 | Mechanistic and functional studies with cell lines expressing PP-1G subunit site-specific mutations will help clarify the exact role and regulation of PP-1G site-specific phosphorylations on PP-1 catalytic function. |
| 331 | 10077352 | A long-term (> or =24 h) exposure of insulin-secreting HIT T15 cells to the phosphatase inhibitor, okadaic acid (OA), at concentrations inhibiting serine/threonine phosphatases 1 (PP1) and 2A (PP2A) reduced proliferation and insulin secretion. |
| 332 | 10585879 | Role of janus kinase-2 in insulin-mediated phosphorylation and inactivation of protein phosphatase-2A and its impact on upstream insulin signalling components. |
| 333 | 10585879 | Our recent studies indicate that insulin rapidly inactivates serine/threonine protein phosphatase-2A (PP-2A) by increasing tyrosine phosphorylation on the catalytic subunit. |
| 334 | 10585879 | The exact mechanism of PP-2A inactivation by insulin in vivo is unclear. |
| 335 | 10585879 | In this study we investigated the potential role of JAK-2 in insulin-mediated tyrosine phosphorylation and inactivation of PP-2A using the rat skeletal muscle cell line L6. |
| 336 | 10585879 | Co-immunoprecipitation studies revealed that PP-2A is associated with JAK-2 in the basal state. |
| 337 | 10585879 | Insulin treatment did not alter JAK-2 association with PP-2A, but did increase JAK-2-mediated tyrosine phosphorylation of the PP-2A catalytic subunit and therefore inhibited PP-2A enzymic activity. |
| 338 | 10585879 | Furthermore, PP-2A is associated with phosphoinositide 3-kinase (PI-3K) in the basal state and insulin treatment increases the catalytic activity of PI-3K bound to PP-2A. |
| 339 | 10585879 | Pretreatment with AG-490, a specific JAK-2 inhibitor, and SpcAMP, a cAMP agonist, prevented the insulin-mediated increase in (i) JAK-2 kinase activity, (ii) PP-2A tyrosine phosphorylation, (iii) PP-2A inactivation and restored the enzyme activity to control levels, and (iv) PP-2A and JAK-2-associated PI-3K activity. |
| 340 | 10585879 | These observations, together with the fact that insulin rapidly activates JAK-2 in L6 cells, and that this is accompanied by an increase in tyrosine phosphorylation of PP-2A in JAK-2 immunoprecipitates, suggest that insulin controls the activation status of PP-2A by tyrosine phosphorylation via JAK-2. |
| 341 | 10585879 | PP-2A inactivation may result in an amplification of insulin-generated signals at the level of PI-3K. |
| 342 | 10585879 | Role of janus kinase-2 in insulin-mediated phosphorylation and inactivation of protein phosphatase-2A and its impact on upstream insulin signalling components. |
| 343 | 10585879 | Our recent studies indicate that insulin rapidly inactivates serine/threonine protein phosphatase-2A (PP-2A) by increasing tyrosine phosphorylation on the catalytic subunit. |
| 344 | 10585879 | The exact mechanism of PP-2A inactivation by insulin in vivo is unclear. |
| 345 | 10585879 | In this study we investigated the potential role of JAK-2 in insulin-mediated tyrosine phosphorylation and inactivation of PP-2A using the rat skeletal muscle cell line L6. |
| 346 | 10585879 | Co-immunoprecipitation studies revealed that PP-2A is associated with JAK-2 in the basal state. |
| 347 | 10585879 | Insulin treatment did not alter JAK-2 association with PP-2A, but did increase JAK-2-mediated tyrosine phosphorylation of the PP-2A catalytic subunit and therefore inhibited PP-2A enzymic activity. |
| 348 | 10585879 | Furthermore, PP-2A is associated with phosphoinositide 3-kinase (PI-3K) in the basal state and insulin treatment increases the catalytic activity of PI-3K bound to PP-2A. |
| 349 | 10585879 | Pretreatment with AG-490, a specific JAK-2 inhibitor, and SpcAMP, a cAMP agonist, prevented the insulin-mediated increase in (i) JAK-2 kinase activity, (ii) PP-2A tyrosine phosphorylation, (iii) PP-2A inactivation and restored the enzyme activity to control levels, and (iv) PP-2A and JAK-2-associated PI-3K activity. |
| 350 | 10585879 | These observations, together with the fact that insulin rapidly activates JAK-2 in L6 cells, and that this is accompanied by an increase in tyrosine phosphorylation of PP-2A in JAK-2 immunoprecipitates, suggest that insulin controls the activation status of PP-2A by tyrosine phosphorylation via JAK-2. |
| 351 | 10585879 | PP-2A inactivation may result in an amplification of insulin-generated signals at the level of PI-3K. |
| 352 | 10585879 | Role of janus kinase-2 in insulin-mediated phosphorylation and inactivation of protein phosphatase-2A and its impact on upstream insulin signalling components. |
| 353 | 10585879 | Our recent studies indicate that insulin rapidly inactivates serine/threonine protein phosphatase-2A (PP-2A) by increasing tyrosine phosphorylation on the catalytic subunit. |
| 354 | 10585879 | The exact mechanism of PP-2A inactivation by insulin in vivo is unclear. |
| 355 | 10585879 | In this study we investigated the potential role of JAK-2 in insulin-mediated tyrosine phosphorylation and inactivation of PP-2A using the rat skeletal muscle cell line L6. |
| 356 | 10585879 | Co-immunoprecipitation studies revealed that PP-2A is associated with JAK-2 in the basal state. |
| 357 | 10585879 | Insulin treatment did not alter JAK-2 association with PP-2A, but did increase JAK-2-mediated tyrosine phosphorylation of the PP-2A catalytic subunit and therefore inhibited PP-2A enzymic activity. |
| 358 | 10585879 | Furthermore, PP-2A is associated with phosphoinositide 3-kinase (PI-3K) in the basal state and insulin treatment increases the catalytic activity of PI-3K bound to PP-2A. |
| 359 | 10585879 | Pretreatment with AG-490, a specific JAK-2 inhibitor, and SpcAMP, a cAMP agonist, prevented the insulin-mediated increase in (i) JAK-2 kinase activity, (ii) PP-2A tyrosine phosphorylation, (iii) PP-2A inactivation and restored the enzyme activity to control levels, and (iv) PP-2A and JAK-2-associated PI-3K activity. |
| 360 | 10585879 | These observations, together with the fact that insulin rapidly activates JAK-2 in L6 cells, and that this is accompanied by an increase in tyrosine phosphorylation of PP-2A in JAK-2 immunoprecipitates, suggest that insulin controls the activation status of PP-2A by tyrosine phosphorylation via JAK-2. |
| 361 | 10585879 | PP-2A inactivation may result in an amplification of insulin-generated signals at the level of PI-3K. |
| 362 | 10585879 | Role of janus kinase-2 in insulin-mediated phosphorylation and inactivation of protein phosphatase-2A and its impact on upstream insulin signalling components. |
| 363 | 10585879 | Our recent studies indicate that insulin rapidly inactivates serine/threonine protein phosphatase-2A (PP-2A) by increasing tyrosine phosphorylation on the catalytic subunit. |
| 364 | 10585879 | The exact mechanism of PP-2A inactivation by insulin in vivo is unclear. |
| 365 | 10585879 | In this study we investigated the potential role of JAK-2 in insulin-mediated tyrosine phosphorylation and inactivation of PP-2A using the rat skeletal muscle cell line L6. |
| 366 | 10585879 | Co-immunoprecipitation studies revealed that PP-2A is associated with JAK-2 in the basal state. |
| 367 | 10585879 | Insulin treatment did not alter JAK-2 association with PP-2A, but did increase JAK-2-mediated tyrosine phosphorylation of the PP-2A catalytic subunit and therefore inhibited PP-2A enzymic activity. |
| 368 | 10585879 | Furthermore, PP-2A is associated with phosphoinositide 3-kinase (PI-3K) in the basal state and insulin treatment increases the catalytic activity of PI-3K bound to PP-2A. |
| 369 | 10585879 | Pretreatment with AG-490, a specific JAK-2 inhibitor, and SpcAMP, a cAMP agonist, prevented the insulin-mediated increase in (i) JAK-2 kinase activity, (ii) PP-2A tyrosine phosphorylation, (iii) PP-2A inactivation and restored the enzyme activity to control levels, and (iv) PP-2A and JAK-2-associated PI-3K activity. |
| 370 | 10585879 | These observations, together with the fact that insulin rapidly activates JAK-2 in L6 cells, and that this is accompanied by an increase in tyrosine phosphorylation of PP-2A in JAK-2 immunoprecipitates, suggest that insulin controls the activation status of PP-2A by tyrosine phosphorylation via JAK-2. |
| 371 | 10585879 | PP-2A inactivation may result in an amplification of insulin-generated signals at the level of PI-3K. |
| 372 | 10585879 | Role of janus kinase-2 in insulin-mediated phosphorylation and inactivation of protein phosphatase-2A and its impact on upstream insulin signalling components. |
| 373 | 10585879 | Our recent studies indicate that insulin rapidly inactivates serine/threonine protein phosphatase-2A (PP-2A) by increasing tyrosine phosphorylation on the catalytic subunit. |
| 374 | 10585879 | The exact mechanism of PP-2A inactivation by insulin in vivo is unclear. |
| 375 | 10585879 | In this study we investigated the potential role of JAK-2 in insulin-mediated tyrosine phosphorylation and inactivation of PP-2A using the rat skeletal muscle cell line L6. |
| 376 | 10585879 | Co-immunoprecipitation studies revealed that PP-2A is associated with JAK-2 in the basal state. |
| 377 | 10585879 | Insulin treatment did not alter JAK-2 association with PP-2A, but did increase JAK-2-mediated tyrosine phosphorylation of the PP-2A catalytic subunit and therefore inhibited PP-2A enzymic activity. |
| 378 | 10585879 | Furthermore, PP-2A is associated with phosphoinositide 3-kinase (PI-3K) in the basal state and insulin treatment increases the catalytic activity of PI-3K bound to PP-2A. |
| 379 | 10585879 | Pretreatment with AG-490, a specific JAK-2 inhibitor, and SpcAMP, a cAMP agonist, prevented the insulin-mediated increase in (i) JAK-2 kinase activity, (ii) PP-2A tyrosine phosphorylation, (iii) PP-2A inactivation and restored the enzyme activity to control levels, and (iv) PP-2A and JAK-2-associated PI-3K activity. |
| 380 | 10585879 | These observations, together with the fact that insulin rapidly activates JAK-2 in L6 cells, and that this is accompanied by an increase in tyrosine phosphorylation of PP-2A in JAK-2 immunoprecipitates, suggest that insulin controls the activation status of PP-2A by tyrosine phosphorylation via JAK-2. |
| 381 | 10585879 | PP-2A inactivation may result in an amplification of insulin-generated signals at the level of PI-3K. |
| 382 | 10585879 | Role of janus kinase-2 in insulin-mediated phosphorylation and inactivation of protein phosphatase-2A and its impact on upstream insulin signalling components. |
| 383 | 10585879 | Our recent studies indicate that insulin rapidly inactivates serine/threonine protein phosphatase-2A (PP-2A) by increasing tyrosine phosphorylation on the catalytic subunit. |
| 384 | 10585879 | The exact mechanism of PP-2A inactivation by insulin in vivo is unclear. |
| 385 | 10585879 | In this study we investigated the potential role of JAK-2 in insulin-mediated tyrosine phosphorylation and inactivation of PP-2A using the rat skeletal muscle cell line L6. |
| 386 | 10585879 | Co-immunoprecipitation studies revealed that PP-2A is associated with JAK-2 in the basal state. |
| 387 | 10585879 | Insulin treatment did not alter JAK-2 association with PP-2A, but did increase JAK-2-mediated tyrosine phosphorylation of the PP-2A catalytic subunit and therefore inhibited PP-2A enzymic activity. |
| 388 | 10585879 | Furthermore, PP-2A is associated with phosphoinositide 3-kinase (PI-3K) in the basal state and insulin treatment increases the catalytic activity of PI-3K bound to PP-2A. |
| 389 | 10585879 | Pretreatment with AG-490, a specific JAK-2 inhibitor, and SpcAMP, a cAMP agonist, prevented the insulin-mediated increase in (i) JAK-2 kinase activity, (ii) PP-2A tyrosine phosphorylation, (iii) PP-2A inactivation and restored the enzyme activity to control levels, and (iv) PP-2A and JAK-2-associated PI-3K activity. |
| 390 | 10585879 | These observations, together with the fact that insulin rapidly activates JAK-2 in L6 cells, and that this is accompanied by an increase in tyrosine phosphorylation of PP-2A in JAK-2 immunoprecipitates, suggest that insulin controls the activation status of PP-2A by tyrosine phosphorylation via JAK-2. |
| 391 | 10585879 | PP-2A inactivation may result in an amplification of insulin-generated signals at the level of PI-3K. |
| 392 | 10585879 | Role of janus kinase-2 in insulin-mediated phosphorylation and inactivation of protein phosphatase-2A and its impact on upstream insulin signalling components. |
| 393 | 10585879 | Our recent studies indicate that insulin rapidly inactivates serine/threonine protein phosphatase-2A (PP-2A) by increasing tyrosine phosphorylation on the catalytic subunit. |
| 394 | 10585879 | The exact mechanism of PP-2A inactivation by insulin in vivo is unclear. |
| 395 | 10585879 | In this study we investigated the potential role of JAK-2 in insulin-mediated tyrosine phosphorylation and inactivation of PP-2A using the rat skeletal muscle cell line L6. |
| 396 | 10585879 | Co-immunoprecipitation studies revealed that PP-2A is associated with JAK-2 in the basal state. |
| 397 | 10585879 | Insulin treatment did not alter JAK-2 association with PP-2A, but did increase JAK-2-mediated tyrosine phosphorylation of the PP-2A catalytic subunit and therefore inhibited PP-2A enzymic activity. |
| 398 | 10585879 | Furthermore, PP-2A is associated with phosphoinositide 3-kinase (PI-3K) in the basal state and insulin treatment increases the catalytic activity of PI-3K bound to PP-2A. |
| 399 | 10585879 | Pretreatment with AG-490, a specific JAK-2 inhibitor, and SpcAMP, a cAMP agonist, prevented the insulin-mediated increase in (i) JAK-2 kinase activity, (ii) PP-2A tyrosine phosphorylation, (iii) PP-2A inactivation and restored the enzyme activity to control levels, and (iv) PP-2A and JAK-2-associated PI-3K activity. |
| 400 | 10585879 | These observations, together with the fact that insulin rapidly activates JAK-2 in L6 cells, and that this is accompanied by an increase in tyrosine phosphorylation of PP-2A in JAK-2 immunoprecipitates, suggest that insulin controls the activation status of PP-2A by tyrosine phosphorylation via JAK-2. |
| 401 | 10585879 | PP-2A inactivation may result in an amplification of insulin-generated signals at the level of PI-3K. |
| 402 | 10585879 | Role of janus kinase-2 in insulin-mediated phosphorylation and inactivation of protein phosphatase-2A and its impact on upstream insulin signalling components. |
| 403 | 10585879 | Our recent studies indicate that insulin rapidly inactivates serine/threonine protein phosphatase-2A (PP-2A) by increasing tyrosine phosphorylation on the catalytic subunit. |
| 404 | 10585879 | The exact mechanism of PP-2A inactivation by insulin in vivo is unclear. |
| 405 | 10585879 | In this study we investigated the potential role of JAK-2 in insulin-mediated tyrosine phosphorylation and inactivation of PP-2A using the rat skeletal muscle cell line L6. |
| 406 | 10585879 | Co-immunoprecipitation studies revealed that PP-2A is associated with JAK-2 in the basal state. |
| 407 | 10585879 | Insulin treatment did not alter JAK-2 association with PP-2A, but did increase JAK-2-mediated tyrosine phosphorylation of the PP-2A catalytic subunit and therefore inhibited PP-2A enzymic activity. |
| 408 | 10585879 | Furthermore, PP-2A is associated with phosphoinositide 3-kinase (PI-3K) in the basal state and insulin treatment increases the catalytic activity of PI-3K bound to PP-2A. |
| 409 | 10585879 | Pretreatment with AG-490, a specific JAK-2 inhibitor, and SpcAMP, a cAMP agonist, prevented the insulin-mediated increase in (i) JAK-2 kinase activity, (ii) PP-2A tyrosine phosphorylation, (iii) PP-2A inactivation and restored the enzyme activity to control levels, and (iv) PP-2A and JAK-2-associated PI-3K activity. |
| 410 | 10585879 | These observations, together with the fact that insulin rapidly activates JAK-2 in L6 cells, and that this is accompanied by an increase in tyrosine phosphorylation of PP-2A in JAK-2 immunoprecipitates, suggest that insulin controls the activation status of PP-2A by tyrosine phosphorylation via JAK-2. |
| 411 | 10585879 | PP-2A inactivation may result in an amplification of insulin-generated signals at the level of PI-3K. |
| 412 | 10585879 | Role of janus kinase-2 in insulin-mediated phosphorylation and inactivation of protein phosphatase-2A and its impact on upstream insulin signalling components. |
| 413 | 10585879 | Our recent studies indicate that insulin rapidly inactivates serine/threonine protein phosphatase-2A (PP-2A) by increasing tyrosine phosphorylation on the catalytic subunit. |
| 414 | 10585879 | The exact mechanism of PP-2A inactivation by insulin in vivo is unclear. |
| 415 | 10585879 | In this study we investigated the potential role of JAK-2 in insulin-mediated tyrosine phosphorylation and inactivation of PP-2A using the rat skeletal muscle cell line L6. |
| 416 | 10585879 | Co-immunoprecipitation studies revealed that PP-2A is associated with JAK-2 in the basal state. |
| 417 | 10585879 | Insulin treatment did not alter JAK-2 association with PP-2A, but did increase JAK-2-mediated tyrosine phosphorylation of the PP-2A catalytic subunit and therefore inhibited PP-2A enzymic activity. |
| 418 | 10585879 | Furthermore, PP-2A is associated with phosphoinositide 3-kinase (PI-3K) in the basal state and insulin treatment increases the catalytic activity of PI-3K bound to PP-2A. |
| 419 | 10585879 | Pretreatment with AG-490, a specific JAK-2 inhibitor, and SpcAMP, a cAMP agonist, prevented the insulin-mediated increase in (i) JAK-2 kinase activity, (ii) PP-2A tyrosine phosphorylation, (iii) PP-2A inactivation and restored the enzyme activity to control levels, and (iv) PP-2A and JAK-2-associated PI-3K activity. |
| 420 | 10585879 | These observations, together with the fact that insulin rapidly activates JAK-2 in L6 cells, and that this is accompanied by an increase in tyrosine phosphorylation of PP-2A in JAK-2 immunoprecipitates, suggest that insulin controls the activation status of PP-2A by tyrosine phosphorylation via JAK-2. |
| 421 | 10585879 | PP-2A inactivation may result in an amplification of insulin-generated signals at the level of PI-3K. |
| 422 | 10585879 | Role of janus kinase-2 in insulin-mediated phosphorylation and inactivation of protein phosphatase-2A and its impact on upstream insulin signalling components. |
| 423 | 10585879 | Our recent studies indicate that insulin rapidly inactivates serine/threonine protein phosphatase-2A (PP-2A) by increasing tyrosine phosphorylation on the catalytic subunit. |
| 424 | 10585879 | The exact mechanism of PP-2A inactivation by insulin in vivo is unclear. |
| 425 | 10585879 | In this study we investigated the potential role of JAK-2 in insulin-mediated tyrosine phosphorylation and inactivation of PP-2A using the rat skeletal muscle cell line L6. |
| 426 | 10585879 | Co-immunoprecipitation studies revealed that PP-2A is associated with JAK-2 in the basal state. |
| 427 | 10585879 | Insulin treatment did not alter JAK-2 association with PP-2A, but did increase JAK-2-mediated tyrosine phosphorylation of the PP-2A catalytic subunit and therefore inhibited PP-2A enzymic activity. |
| 428 | 10585879 | Furthermore, PP-2A is associated with phosphoinositide 3-kinase (PI-3K) in the basal state and insulin treatment increases the catalytic activity of PI-3K bound to PP-2A. |
| 429 | 10585879 | Pretreatment with AG-490, a specific JAK-2 inhibitor, and SpcAMP, a cAMP agonist, prevented the insulin-mediated increase in (i) JAK-2 kinase activity, (ii) PP-2A tyrosine phosphorylation, (iii) PP-2A inactivation and restored the enzyme activity to control levels, and (iv) PP-2A and JAK-2-associated PI-3K activity. |
| 430 | 10585879 | These observations, together with the fact that insulin rapidly activates JAK-2 in L6 cells, and that this is accompanied by an increase in tyrosine phosphorylation of PP-2A in JAK-2 immunoprecipitates, suggest that insulin controls the activation status of PP-2A by tyrosine phosphorylation via JAK-2. |
| 431 | 10585879 | PP-2A inactivation may result in an amplification of insulin-generated signals at the level of PI-3K. |
| 432 | 10625950 | Inositol hexakisphosphate (InsP6) inhibits serine/threonine protein phosphatases type-1 (PP1), type-2A (PP2A) and type-3 (PP3) in a concentration-dependent manner. |
| 433 | 10854420 | Activation of malonyl-CoA decarboxylase in rat skeletal muscle by contraction and the AMP-activated protein kinase activator 5-aminoimidazole-4-carboxamide-1-beta -D-ribofuranoside. |
| 434 | 10854420 | During contraction decreases in muscle malonyl-CoA concentration have been related to activation of AMP-activated protein kinase (AMPK), which phosphorylates and inhibits acetyl-CoA carboxylase (ACC), the rate-limiting enzyme in malonyl-CoA formation. |
| 435 | 10854420 | The increase in MCD activity was markedly diminished when immunopurified enzyme was treated with protein phosphatase 2A or when phosphatase inhibitors were omitted from the homogenizing solution and assay mixture. |
| 436 | 10854420 | Incubation of extensor digitorum longus muscle for 1 h with 2 mm 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside, a cell-permeable activator of AMPK, increased MCD activity 2-fold. |
| 437 | 10854420 | Here, too, addition of protein phosphatase 2A to the immunopellets reversed the increase of MCD activity. |
| 438 | 10854420 | The results strongly suggest that activation of AMPK during muscle contraction leads to phosphorylation of MCD and an increase in its activity. |
| 439 | 10854420 | They also suggest a dual control of malonyl-CoA concentration by ACC and MCD, via AMPK, during exercise. |
| 440 | 10854420 | Activation of malonyl-CoA decarboxylase in rat skeletal muscle by contraction and the AMP-activated protein kinase activator 5-aminoimidazole-4-carboxamide-1-beta -D-ribofuranoside. |
| 441 | 10854420 | During contraction decreases in muscle malonyl-CoA concentration have been related to activation of AMP-activated protein kinase (AMPK), which phosphorylates and inhibits acetyl-CoA carboxylase (ACC), the rate-limiting enzyme in malonyl-CoA formation. |
| 442 | 10854420 | The increase in MCD activity was markedly diminished when immunopurified enzyme was treated with protein phosphatase 2A or when phosphatase inhibitors were omitted from the homogenizing solution and assay mixture. |
| 443 | 10854420 | Incubation of extensor digitorum longus muscle for 1 h with 2 mm 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside, a cell-permeable activator of AMPK, increased MCD activity 2-fold. |
| 444 | 10854420 | Here, too, addition of protein phosphatase 2A to the immunopellets reversed the increase of MCD activity. |
| 445 | 10854420 | The results strongly suggest that activation of AMPK during muscle contraction leads to phosphorylation of MCD and an increase in its activity. |
| 446 | 10854420 | They also suggest a dual control of malonyl-CoA concentration by ACC and MCD, via AMPK, during exercise. |
| 447 | 11423479 | ACC stimulation by glutamate and magnesium was maximally demonstrable in the cytosolic fraction; it was markedly reduced by okadaic acid (OKA) in concentrations (<50 nmol/l) that inhibited protein phosphatase 2A (PP2A). |
| 448 | 11423479 | Furthermore, pretreatment of the cytosolic fraction with anti-PP2A serum attenuated the glutamate- and magnesium-mediated activation of ACC, thereby suggesting that ACC may be regulated by an OKA-sensitive PP2A-like enzyme. |
| 449 | 11423479 | Streptavidin-agarose chromatography studies have indicated that glutamate- and magnesium-mediated effects on ACC are attributable to activation of ACC's dephosphorylation; this suggests that the stimulatory effects of glutamate and magnesium on ACC might involve activation of an OKA-sensitive PP2A-like enzyme that dephosphorylates and activates ACC. |
| 450 | 11423479 | In our study, 5-amino-imidazolecarboxamide (AICA) riboside, a stimulator of AMP kinase, significantly inhibited glucose-mediated activation of ACC and insulin secretion from isolated beta-cells. |
| 451 | 11423479 | Together, our data provide evidence for a unique regulatory mechanism for the activation of ACC in the pancreatic beta-cell, leading to the generation of physiological signals that may be relevant for physiological insulin secretion. |
| 452 | 11423479 | ACC stimulation by glutamate and magnesium was maximally demonstrable in the cytosolic fraction; it was markedly reduced by okadaic acid (OKA) in concentrations (<50 nmol/l) that inhibited protein phosphatase 2A (PP2A). |
| 453 | 11423479 | Furthermore, pretreatment of the cytosolic fraction with anti-PP2A serum attenuated the glutamate- and magnesium-mediated activation of ACC, thereby suggesting that ACC may be regulated by an OKA-sensitive PP2A-like enzyme. |
| 454 | 11423479 | Streptavidin-agarose chromatography studies have indicated that glutamate- and magnesium-mediated effects on ACC are attributable to activation of ACC's dephosphorylation; this suggests that the stimulatory effects of glutamate and magnesium on ACC might involve activation of an OKA-sensitive PP2A-like enzyme that dephosphorylates and activates ACC. |
| 455 | 11423479 | In our study, 5-amino-imidazolecarboxamide (AICA) riboside, a stimulator of AMP kinase, significantly inhibited glucose-mediated activation of ACC and insulin secretion from isolated beta-cells. |
| 456 | 11423479 | Together, our data provide evidence for a unique regulatory mechanism for the activation of ACC in the pancreatic beta-cell, leading to the generation of physiological signals that may be relevant for physiological insulin secretion. |
| 457 | 11423479 | ACC stimulation by glutamate and magnesium was maximally demonstrable in the cytosolic fraction; it was markedly reduced by okadaic acid (OKA) in concentrations (<50 nmol/l) that inhibited protein phosphatase 2A (PP2A). |
| 458 | 11423479 | Furthermore, pretreatment of the cytosolic fraction with anti-PP2A serum attenuated the glutamate- and magnesium-mediated activation of ACC, thereby suggesting that ACC may be regulated by an OKA-sensitive PP2A-like enzyme. |
| 459 | 11423479 | Streptavidin-agarose chromatography studies have indicated that glutamate- and magnesium-mediated effects on ACC are attributable to activation of ACC's dephosphorylation; this suggests that the stimulatory effects of glutamate and magnesium on ACC might involve activation of an OKA-sensitive PP2A-like enzyme that dephosphorylates and activates ACC. |
| 460 | 11423479 | In our study, 5-amino-imidazolecarboxamide (AICA) riboside, a stimulator of AMP kinase, significantly inhibited glucose-mediated activation of ACC and insulin secretion from isolated beta-cells. |
| 461 | 11423479 | Together, our data provide evidence for a unique regulatory mechanism for the activation of ACC in the pancreatic beta-cell, leading to the generation of physiological signals that may be relevant for physiological insulin secretion. |
| 462 | 11574400 | A role for protein phosphatase 2A-like activity, but not atypical protein kinase Czeta, in the inhibition of protein kinase B/Akt and glycogen synthesis by palmitate. |
| 463 | 11574400 | We have shown previously that palmitate treatment of C2C12 skeletal muscle myotubes causes inhibition of the protein kinase B (PKB) pathway and hence reduces insulin-stimulated glycogen synthesis through the elevation of intracellular ceramide levels. |
| 464 | 11574400 | Ceramide is known to activate both atypical protein kinase C (aPKC) zeta and protein phosphatase (PP) 2A, and each of these effectors has been reported to inhibit PKB. |
| 465 | 11574400 | Incubation with the phosphatase inhibitor okadaic acid before insulin stimulation protected against the effect of the fatty acid on PKB phosphorylation. |
| 466 | 11574400 | We conclude that palmitate disrupts insulin signaling in C2C12 myotubes by promoting PP2A-like activity and, therefore, the dephosphorylation of PKB, which in turn reduces the stimulation of glycogen synthesis. |
| 467 | 11574400 | A role for protein phosphatase 2A-like activity, but not atypical protein kinase Czeta, in the inhibition of protein kinase B/Akt and glycogen synthesis by palmitate. |
| 468 | 11574400 | We have shown previously that palmitate treatment of C2C12 skeletal muscle myotubes causes inhibition of the protein kinase B (PKB) pathway and hence reduces insulin-stimulated glycogen synthesis through the elevation of intracellular ceramide levels. |
| 469 | 11574400 | Ceramide is known to activate both atypical protein kinase C (aPKC) zeta and protein phosphatase (PP) 2A, and each of these effectors has been reported to inhibit PKB. |
| 470 | 11574400 | Incubation with the phosphatase inhibitor okadaic acid before insulin stimulation protected against the effect of the fatty acid on PKB phosphorylation. |
| 471 | 11574400 | We conclude that palmitate disrupts insulin signaling in C2C12 myotubes by promoting PP2A-like activity and, therefore, the dephosphorylation of PKB, which in turn reduces the stimulation of glycogen synthesis. |
| 472 | 11679435 | Ceramide mediates insulin resistance by tumor necrosis factor-alpha in brown adipocytes by maintaining Akt in an inactive dephosphorylated state. |
| 473 | 11679435 | Tumor necrosis factor (TNF)-alpha causes insulin resistance on glucose uptake in fetal brown adipocytes. |
| 474 | 11679435 | A short-chain ceramide analog, C2-ceramide, completely precluded insulin-stimulated glucose uptake and insulin-induced GLUT4 translocation to plasma membrane, as determined by Western blot or immunofluorescent localization of GLUT4. |
| 475 | 11679435 | Analysis of the phosphatidylinositol (PI) 3-kinase signaling pathway indicated that C2-ceramide precluded insulin stimulation of Akt kinase activity, but not of PI-3 kinase or protein kinase C-zeta activity. |
| 476 | 11679435 | C2-ceramide completely abolished insulin-stimulated Akt/protein kinase B phosphorylation on regulatory residues Thr 308 and Ser 473, as did TNF-alpha, and inhibited insulin-induced mobility shift in Akt1 and Akt2 separated in PAGE. |
| 477 | 11679435 | Moreover, C2-ceramide seemed to activate a protein phosphatase (PP) involved in dephosphorylating Akt because 1) PP2A activity was increased in C2-ceramide- and TNF-alpha-treated cells, 2) treatment with okadaic acid concomitantly with C2-ceramide completely restored Akt phosphorylation by insulin, and 3) transient transfection of a constitutively active form of Akt did not restore Akt activity. |
| 478 | 11679435 | Our results indicate that ceramide produced by TNF-alpha induces insulin resistance in brown adipocytes by maintaining Akt in an inactive dephosphorylated state. |
| 479 | 12079844 | Protein kinase C and lipid-induced insulin resistance in skeletal muscle. |
| 480 | 12079844 | Thus, increased diacylglycerol levels in muscle are associated with the activation of one or more isoforms of the protein kinase C family, which is known to attenuate insulin signaling, especially at the level of IRS-1. |
| 481 | 12079844 | In addition, de novo synthesis of ceramide can inhibit more distal sites by the activation of protein phosphatase 2A and hence promote the dephosphorylation and inactivation of protein kinase B. |
| 482 | 12175701 | Both protein phosphatase-1 (PP-1) and PP-2A inhibit cAMP-mediated increases in transcription by dephosphorylating CREB at ser-133. |
| 483 | 12175701 | Western blot analysis indicated that protein phosphatase 1 (PP-1) was expressed constitutively in palatal tissue during its development. |
| 484 | 12175701 | Virtually all phosphatase activity in the tissue extracts could be inhibited by 5 microM okadaic acid, demonstrating that PP-1 and PP-2A account for all detectable ser/thr protein phosphatase activity present in the developing palate. |
| 485 | 12175701 | Moreover, no significant differences in PP-1 and PP-2A activities were observed during the period of palate development. |
| 486 | 12175701 | Treatment of primary cultures of murine embryonic palate mesenchymal (MEPM) cells with forskolin (20 microM) to elevate intracellular cAMP levels, resulted in a time-dependent increase in CREB ser-133 phosphorylation and a corresponding time dependent decrease in PP-1 and PP-2A levels. |
| 487 | 12175701 | This suggests that PP-1 activity may contribute to transcriptional regulation of CREB and that PP-1 and PP-2A are regulated differentially by cAMP. |
| 488 | 12175701 | Treatment of MEPM cells with TGF beta 1 (1 ng/ml) under conditions of TGF beta-induced CREB phosphorylation resulted in no effect on the expression of either PP-1 or PP-2A proteins and no significant alterations in total basal protein phosphatase activity. |
| 489 | 12175701 | Both protein phosphatase-1 (PP-1) and PP-2A inhibit cAMP-mediated increases in transcription by dephosphorylating CREB at ser-133. |
| 490 | 12175701 | Western blot analysis indicated that protein phosphatase 1 (PP-1) was expressed constitutively in palatal tissue during its development. |
| 491 | 12175701 | Virtually all phosphatase activity in the tissue extracts could be inhibited by 5 microM okadaic acid, demonstrating that PP-1 and PP-2A account for all detectable ser/thr protein phosphatase activity present in the developing palate. |
| 492 | 12175701 | Moreover, no significant differences in PP-1 and PP-2A activities were observed during the period of palate development. |
| 493 | 12175701 | Treatment of primary cultures of murine embryonic palate mesenchymal (MEPM) cells with forskolin (20 microM) to elevate intracellular cAMP levels, resulted in a time-dependent increase in CREB ser-133 phosphorylation and a corresponding time dependent decrease in PP-1 and PP-2A levels. |
| 494 | 12175701 | This suggests that PP-1 activity may contribute to transcriptional regulation of CREB and that PP-1 and PP-2A are regulated differentially by cAMP. |
| 495 | 12175701 | Treatment of MEPM cells with TGF beta 1 (1 ng/ml) under conditions of TGF beta-induced CREB phosphorylation resulted in no effect on the expression of either PP-1 or PP-2A proteins and no significant alterations in total basal protein phosphatase activity. |
| 496 | 12175701 | Both protein phosphatase-1 (PP-1) and PP-2A inhibit cAMP-mediated increases in transcription by dephosphorylating CREB at ser-133. |
| 497 | 12175701 | Western blot analysis indicated that protein phosphatase 1 (PP-1) was expressed constitutively in palatal tissue during its development. |
| 498 | 12175701 | Virtually all phosphatase activity in the tissue extracts could be inhibited by 5 microM okadaic acid, demonstrating that PP-1 and PP-2A account for all detectable ser/thr protein phosphatase activity present in the developing palate. |
| 499 | 12175701 | Moreover, no significant differences in PP-1 and PP-2A activities were observed during the period of palate development. |
| 500 | 12175701 | Treatment of primary cultures of murine embryonic palate mesenchymal (MEPM) cells with forskolin (20 microM) to elevate intracellular cAMP levels, resulted in a time-dependent increase in CREB ser-133 phosphorylation and a corresponding time dependent decrease in PP-1 and PP-2A levels. |
| 501 | 12175701 | This suggests that PP-1 activity may contribute to transcriptional regulation of CREB and that PP-1 and PP-2A are regulated differentially by cAMP. |
| 502 | 12175701 | Treatment of MEPM cells with TGF beta 1 (1 ng/ml) under conditions of TGF beta-induced CREB phosphorylation resulted in no effect on the expression of either PP-1 or PP-2A proteins and no significant alterations in total basal protein phosphatase activity. |
| 503 | 12175701 | Both protein phosphatase-1 (PP-1) and PP-2A inhibit cAMP-mediated increases in transcription by dephosphorylating CREB at ser-133. |
| 504 | 12175701 | Western blot analysis indicated that protein phosphatase 1 (PP-1) was expressed constitutively in palatal tissue during its development. |
| 505 | 12175701 | Virtually all phosphatase activity in the tissue extracts could be inhibited by 5 microM okadaic acid, demonstrating that PP-1 and PP-2A account for all detectable ser/thr protein phosphatase activity present in the developing palate. |
| 506 | 12175701 | Moreover, no significant differences in PP-1 and PP-2A activities were observed during the period of palate development. |
| 507 | 12175701 | Treatment of primary cultures of murine embryonic palate mesenchymal (MEPM) cells with forskolin (20 microM) to elevate intracellular cAMP levels, resulted in a time-dependent increase in CREB ser-133 phosphorylation and a corresponding time dependent decrease in PP-1 and PP-2A levels. |
| 508 | 12175701 | This suggests that PP-1 activity may contribute to transcriptional regulation of CREB and that PP-1 and PP-2A are regulated differentially by cAMP. |
| 509 | 12175701 | Treatment of MEPM cells with TGF beta 1 (1 ng/ml) under conditions of TGF beta-induced CREB phosphorylation resulted in no effect on the expression of either PP-1 or PP-2A proteins and no significant alterations in total basal protein phosphatase activity. |
| 510 | 12175701 | Both protein phosphatase-1 (PP-1) and PP-2A inhibit cAMP-mediated increases in transcription by dephosphorylating CREB at ser-133. |
| 511 | 12175701 | Western blot analysis indicated that protein phosphatase 1 (PP-1) was expressed constitutively in palatal tissue during its development. |
| 512 | 12175701 | Virtually all phosphatase activity in the tissue extracts could be inhibited by 5 microM okadaic acid, demonstrating that PP-1 and PP-2A account for all detectable ser/thr protein phosphatase activity present in the developing palate. |
| 513 | 12175701 | Moreover, no significant differences in PP-1 and PP-2A activities were observed during the period of palate development. |
| 514 | 12175701 | Treatment of primary cultures of murine embryonic palate mesenchymal (MEPM) cells with forskolin (20 microM) to elevate intracellular cAMP levels, resulted in a time-dependent increase in CREB ser-133 phosphorylation and a corresponding time dependent decrease in PP-1 and PP-2A levels. |
| 515 | 12175701 | This suggests that PP-1 activity may contribute to transcriptional regulation of CREB and that PP-1 and PP-2A are regulated differentially by cAMP. |
| 516 | 12175701 | Treatment of MEPM cells with TGF beta 1 (1 ng/ml) under conditions of TGF beta-induced CREB phosphorylation resulted in no effect on the expression of either PP-1 or PP-2A proteins and no significant alterations in total basal protein phosphatase activity. |
| 517 | 12175701 | Both protein phosphatase-1 (PP-1) and PP-2A inhibit cAMP-mediated increases in transcription by dephosphorylating CREB at ser-133. |
| 518 | 12175701 | Western blot analysis indicated that protein phosphatase 1 (PP-1) was expressed constitutively in palatal tissue during its development. |
| 519 | 12175701 | Virtually all phosphatase activity in the tissue extracts could be inhibited by 5 microM okadaic acid, demonstrating that PP-1 and PP-2A account for all detectable ser/thr protein phosphatase activity present in the developing palate. |
| 520 | 12175701 | Moreover, no significant differences in PP-1 and PP-2A activities were observed during the period of palate development. |
| 521 | 12175701 | Treatment of primary cultures of murine embryonic palate mesenchymal (MEPM) cells with forskolin (20 microM) to elevate intracellular cAMP levels, resulted in a time-dependent increase in CREB ser-133 phosphorylation and a corresponding time dependent decrease in PP-1 and PP-2A levels. |
| 522 | 12175701 | This suggests that PP-1 activity may contribute to transcriptional regulation of CREB and that PP-1 and PP-2A are regulated differentially by cAMP. |
| 523 | 12175701 | Treatment of MEPM cells with TGF beta 1 (1 ng/ml) under conditions of TGF beta-induced CREB phosphorylation resulted in no effect on the expression of either PP-1 or PP-2A proteins and no significant alterations in total basal protein phosphatase activity. |
| 524 | 12205083 | Western blotting revealed that dopamine increased the association of dynamin-2 with the plasma membrane and with phosphatidylinositol 3-kinase. |
| 525 | 12205083 | Dopamine increased protein phosphatase 2A activity and dephosphorylated dynamin-2. |
| 526 | 12205083 | In cells expressing a dominant-negative mutant of protein phosphatase 2A, dopamine failed to dephosphorylate dynamin-2 and to reduce Na(+),K(+)-ATPase activity. |
| 527 | 12205083 | These results demonstrate a distinct signaling network originating from the dopamine receptor that regulates the state of dynamin-2 phosphorylation and that promotes its location (by interaction with phosphatidylinositol 3-kinase) at the site of Na(+),K(+)-ATPase endocytosis. |
| 528 | 12205083 | Western blotting revealed that dopamine increased the association of dynamin-2 with the plasma membrane and with phosphatidylinositol 3-kinase. |
| 529 | 12205083 | Dopamine increased protein phosphatase 2A activity and dephosphorylated dynamin-2. |
| 530 | 12205083 | In cells expressing a dominant-negative mutant of protein phosphatase 2A, dopamine failed to dephosphorylate dynamin-2 and to reduce Na(+),K(+)-ATPase activity. |
| 531 | 12205083 | These results demonstrate a distinct signaling network originating from the dopamine receptor that regulates the state of dynamin-2 phosphorylation and that promotes its location (by interaction with phosphatidylinositol 3-kinase) at the site of Na(+),K(+)-ATPase endocytosis. |
| 532 | 12534451 | Effect of insulin on protein phosphatase 2A expression in muscle in type 2 diabetes. |
| 533 | 15090261 | PKC, PP2A, COX-2, 5-lipooxygenase, nitric oxide synthase, NADPH-oxidase, superoxide dismutase, phopholipase A2) and modulates the expression of genes that are involved in atherosclerosis (e.g. scavenger receptors, integrins, selectins, cytokines, cyclins). |
| 534 | 15805588 | We previously identified and characterized a glutamate- and magnesium-sensitive PP2A-like phosphatase (GAPP), which dephosphorylated and activated acetyl-CoA carboxylase (ACC) in the islet beta cell. |
| 535 | 15805588 | Together, our findings raise an interesting possibility that inhibition of GAPP-catalyzed inactivation of ACC (and subsequent reduction in the generation of long-chain fatty acids) could contribute toward the abnormalities in insulin secretion demonstrable in this animal model for type 2 diabetes. |
| 536 | 15935144 | Emerging evidence implicates protein phosphatase 2A (PP2A) in the phenomenon of insulin secretion. |
| 537 | 15935144 | The three principal objectives of this commentary are to: (i) review the existing evidence, which suggests regulation, by glucose and other insulin secretagogues, of PP2A in the beta cell; (ii) discuss the experimental evidence, which implicates PP2A-like enzymes in the dephosphorylation and inactivation of key beta cell phosphoprotein substrates (e.g., Akt and Bcl-2), which may be necessary for beta cell proliferation and survival, culminating in the loss of the beta cell mass; and (iii) highlight potential avenues for future research, including the development of specific pharmacological and therapeutic interventional modalities for the inhibition of specific PP2A-like phosphatases for the prevention of loss of beta cell mass leading to the onset of diabetes. |
| 538 | 15935144 | Emerging evidence implicates protein phosphatase 2A (PP2A) in the phenomenon of insulin secretion. |
| 539 | 15935144 | The three principal objectives of this commentary are to: (i) review the existing evidence, which suggests regulation, by glucose and other insulin secretagogues, of PP2A in the beta cell; (ii) discuss the experimental evidence, which implicates PP2A-like enzymes in the dephosphorylation and inactivation of key beta cell phosphoprotein substrates (e.g., Akt and Bcl-2), which may be necessary for beta cell proliferation and survival, culminating in the loss of the beta cell mass; and (iii) highlight potential avenues for future research, including the development of specific pharmacological and therapeutic interventional modalities for the inhibition of specific PP2A-like phosphatases for the prevention of loss of beta cell mass leading to the onset of diabetes. |
| 540 | 16006680 | Role played by protein phosphatase 2A in insulin secretion. |
| 541 | 16006680 | This review focuses on the importance of protein phosphatase 2A in insulin secretion. |
| 542 | 16006680 | The ability of protein phosphatase 2A to change its activity in the presence of glucose and inhibitors provides clues to its role in regulating insulin secretion. |
| 543 | 16006680 | Characterizing protein phosphatase 2A within the beta-cell will certainly help us in understanding the mechanisms involved in insulin secretion and provide valuable information for drug development. |
| 544 | 16006680 | Role played by protein phosphatase 2A in insulin secretion. |
| 545 | 16006680 | This review focuses on the importance of protein phosphatase 2A in insulin secretion. |
| 546 | 16006680 | The ability of protein phosphatase 2A to change its activity in the presence of glucose and inhibitors provides clues to its role in regulating insulin secretion. |
| 547 | 16006680 | Characterizing protein phosphatase 2A within the beta-cell will certainly help us in understanding the mechanisms involved in insulin secretion and provide valuable information for drug development. |
| 548 | 16006680 | Role played by protein phosphatase 2A in insulin secretion. |
| 549 | 16006680 | This review focuses on the importance of protein phosphatase 2A in insulin secretion. |
| 550 | 16006680 | The ability of protein phosphatase 2A to change its activity in the presence of glucose and inhibitors provides clues to its role in regulating insulin secretion. |
| 551 | 16006680 | Characterizing protein phosphatase 2A within the beta-cell will certainly help us in understanding the mechanisms involved in insulin secretion and provide valuable information for drug development. |
| 552 | 16006680 | Role played by protein phosphatase 2A in insulin secretion. |
| 553 | 16006680 | This review focuses on the importance of protein phosphatase 2A in insulin secretion. |
| 554 | 16006680 | The ability of protein phosphatase 2A to change its activity in the presence of glucose and inhibitors provides clues to its role in regulating insulin secretion. |
| 555 | 16006680 | Characterizing protein phosphatase 2A within the beta-cell will certainly help us in understanding the mechanisms involved in insulin secretion and provide valuable information for drug development. |
| 556 | 16392682 | In addition to the phenotypic alterations, the enhancement for phosphorylation of extracellular signal-regulated kinase (ERK) protein was observed in the FR177391-treated 3T3-L1 cells. |
| 557 | 16392682 | These results suggest that prolonged activation of ERK protein due to inhibition of its dephosphorylation by PP2A plays an important role in adipocyte maturation and regulation of the blood revels of lipids. |
| 558 | 16679742 | The nuclear receptor constitutive androstane receptor (CAR), a key transcription factor for the expression of cytochrome P450 (CYP) 2B genes, resides in the cytoplasm under untreated conditions and translocates into the nucleus upon xenobiotic exposure. |
| 559 | 16679742 | CAR forms a multiprotein complex including heat shock protein 90 in the cytoplasm as the glucocorticoid receptor, and it is likely that protein phosphatase 2A plays a critical role in the first step of CAR nuclear translocation. |
| 560 | 16679742 | In obese mice fed a high-fat diet, however, hepatic CYP3A levels are drastically decreased without any significant changes in the expression of nuclear receptors including the pregnane X receptor and hepatocyte nuclear factor-4, which are known to be key transcription factors in the expression of CYP3A genes. |
| 561 | 17130475 | Therefore, we tested the hypothesis that insulin depletion caused by administration of streptozotocin may cause tau hyperphosphorylation in mouse brain by using site-specific phosphorylation-dependent tau antibodies to obtain precise identification of the phosphorylation of tau on individual residues. |
| 562 | 17130475 | A massive (fivefold average increase) and widespread at multiple residues (detected with eight different phosphorylation-dependent tau antibodies) increase in the phosphorylation of tau was found in mouse cerebral cortex and hippocampus within 3 days of insulin depletion by streptozotocin treatment. |
| 563 | 17130475 | This hyperphosphorylation of tau at some sites was rapidly reversible by peripheral insulin administration. |
| 564 | 17130475 | Examination of several kinases that phosphorylate tau indicated that they were unlikely to account for the widespread hyperphosphorylation of tau caused by streptozotocin treatment, but there was a large decrease in mouse brain protein phosphatase 2A activity, which is known to mediate tau phosphorylation. |
| 565 | 17130475 | These results show that insulin deficiency causes rapid and large increases in tau phosphorylation, a condition that could prime tau for the neuropathology of Alzheimer's disease, thereby contributing to the increased susceptibility to Alzheimer's disease caused by diabetes. |
| 566 | 17255104 | Activation of protein phosphatase 2A by palmitate inhibits AMP-activated protein kinase. |
| 567 | 17255104 | Further, in LKB1-deficient cells, palmitate suppressed AMPK-Thr(172) implying that the inhibitory effects of palmitate on AMPK might be independent of LKB1. |
| 568 | 17255104 | Inhibition of PP2A with either okadaic acid, a selective PP2A inhibitor, or PP2A small interference RNA abolished palmitate-induced inhibition on AMPK-Thr(172) phosphorylation. |
| 569 | 17255104 | Conversely, fumonisin B1, which selectively inhibits ceramide synthase and decreases de novo formation of ceramide, abolished the effects of palmitate on both PP2A and AMPK. |
| 570 | 17255104 | Inhibition of AMPK in parallel with increased PP2A activity was founded in C57BL/6J mice fed with high fat diet (HFD) rich in palmitate but not in mice fed with HFD rich in oleate. |
| 571 | 17255104 | Moreover, inhibition of PP2A with PP2A-specific siRNA but not scrambled siRNA reversed HFD-induced inhibition on the phosphorylation of AMPK-Thr(172) and endothelial nitric-oxide synthase (eNOS)-Ser(1177) in mice fed with high fat diets. |
| 572 | 17255104 | Taken together, we conclude that palmitate inhibits the phosphorylation of both AMPK and endothelial nitric-oxide synthase in endothelial cells via ceramide-dependent PP2A activation. |
| 573 | 17255104 | Activation of protein phosphatase 2A by palmitate inhibits AMP-activated protein kinase. |
| 574 | 17255104 | Further, in LKB1-deficient cells, palmitate suppressed AMPK-Thr(172) implying that the inhibitory effects of palmitate on AMPK might be independent of LKB1. |
| 575 | 17255104 | Inhibition of PP2A with either okadaic acid, a selective PP2A inhibitor, or PP2A small interference RNA abolished palmitate-induced inhibition on AMPK-Thr(172) phosphorylation. |
| 576 | 17255104 | Conversely, fumonisin B1, which selectively inhibits ceramide synthase and decreases de novo formation of ceramide, abolished the effects of palmitate on both PP2A and AMPK. |
| 577 | 17255104 | Inhibition of AMPK in parallel with increased PP2A activity was founded in C57BL/6J mice fed with high fat diet (HFD) rich in palmitate but not in mice fed with HFD rich in oleate. |
| 578 | 17255104 | Moreover, inhibition of PP2A with PP2A-specific siRNA but not scrambled siRNA reversed HFD-induced inhibition on the phosphorylation of AMPK-Thr(172) and endothelial nitric-oxide synthase (eNOS)-Ser(1177) in mice fed with high fat diets. |
| 579 | 17255104 | Taken together, we conclude that palmitate inhibits the phosphorylation of both AMPK and endothelial nitric-oxide synthase in endothelial cells via ceramide-dependent PP2A activation. |
| 580 | 17255104 | Activation of protein phosphatase 2A by palmitate inhibits AMP-activated protein kinase. |
| 581 | 17255104 | Further, in LKB1-deficient cells, palmitate suppressed AMPK-Thr(172) implying that the inhibitory effects of palmitate on AMPK might be independent of LKB1. |
| 582 | 17255104 | Inhibition of PP2A with either okadaic acid, a selective PP2A inhibitor, or PP2A small interference RNA abolished palmitate-induced inhibition on AMPK-Thr(172) phosphorylation. |
| 583 | 17255104 | Conversely, fumonisin B1, which selectively inhibits ceramide synthase and decreases de novo formation of ceramide, abolished the effects of palmitate on both PP2A and AMPK. |
| 584 | 17255104 | Inhibition of AMPK in parallel with increased PP2A activity was founded in C57BL/6J mice fed with high fat diet (HFD) rich in palmitate but not in mice fed with HFD rich in oleate. |
| 585 | 17255104 | Moreover, inhibition of PP2A with PP2A-specific siRNA but not scrambled siRNA reversed HFD-induced inhibition on the phosphorylation of AMPK-Thr(172) and endothelial nitric-oxide synthase (eNOS)-Ser(1177) in mice fed with high fat diets. |
| 586 | 17255104 | Taken together, we conclude that palmitate inhibits the phosphorylation of both AMPK and endothelial nitric-oxide synthase in endothelial cells via ceramide-dependent PP2A activation. |
| 587 | 17255104 | Activation of protein phosphatase 2A by palmitate inhibits AMP-activated protein kinase. |
| 588 | 17255104 | Further, in LKB1-deficient cells, palmitate suppressed AMPK-Thr(172) implying that the inhibitory effects of palmitate on AMPK might be independent of LKB1. |
| 589 | 17255104 | Inhibition of PP2A with either okadaic acid, a selective PP2A inhibitor, or PP2A small interference RNA abolished palmitate-induced inhibition on AMPK-Thr(172) phosphorylation. |
| 590 | 17255104 | Conversely, fumonisin B1, which selectively inhibits ceramide synthase and decreases de novo formation of ceramide, abolished the effects of palmitate on both PP2A and AMPK. |
| 591 | 17255104 | Inhibition of AMPK in parallel with increased PP2A activity was founded in C57BL/6J mice fed with high fat diet (HFD) rich in palmitate but not in mice fed with HFD rich in oleate. |
| 592 | 17255104 | Moreover, inhibition of PP2A with PP2A-specific siRNA but not scrambled siRNA reversed HFD-induced inhibition on the phosphorylation of AMPK-Thr(172) and endothelial nitric-oxide synthase (eNOS)-Ser(1177) in mice fed with high fat diets. |
| 593 | 17255104 | Taken together, we conclude that palmitate inhibits the phosphorylation of both AMPK and endothelial nitric-oxide synthase in endothelial cells via ceramide-dependent PP2A activation. |
| 594 | 17255104 | Activation of protein phosphatase 2A by palmitate inhibits AMP-activated protein kinase. |
| 595 | 17255104 | Further, in LKB1-deficient cells, palmitate suppressed AMPK-Thr(172) implying that the inhibitory effects of palmitate on AMPK might be independent of LKB1. |
| 596 | 17255104 | Inhibition of PP2A with either okadaic acid, a selective PP2A inhibitor, or PP2A small interference RNA abolished palmitate-induced inhibition on AMPK-Thr(172) phosphorylation. |
| 597 | 17255104 | Conversely, fumonisin B1, which selectively inhibits ceramide synthase and decreases de novo formation of ceramide, abolished the effects of palmitate on both PP2A and AMPK. |
| 598 | 17255104 | Inhibition of AMPK in parallel with increased PP2A activity was founded in C57BL/6J mice fed with high fat diet (HFD) rich in palmitate but not in mice fed with HFD rich in oleate. |
| 599 | 17255104 | Moreover, inhibition of PP2A with PP2A-specific siRNA but not scrambled siRNA reversed HFD-induced inhibition on the phosphorylation of AMPK-Thr(172) and endothelial nitric-oxide synthase (eNOS)-Ser(1177) in mice fed with high fat diets. |
| 600 | 17255104 | Taken together, we conclude that palmitate inhibits the phosphorylation of both AMPK and endothelial nitric-oxide synthase in endothelial cells via ceramide-dependent PP2A activation. |
| 601 | 17255104 | Activation of protein phosphatase 2A by palmitate inhibits AMP-activated protein kinase. |
| 602 | 17255104 | Further, in LKB1-deficient cells, palmitate suppressed AMPK-Thr(172) implying that the inhibitory effects of palmitate on AMPK might be independent of LKB1. |
| 603 | 17255104 | Inhibition of PP2A with either okadaic acid, a selective PP2A inhibitor, or PP2A small interference RNA abolished palmitate-induced inhibition on AMPK-Thr(172) phosphorylation. |
| 604 | 17255104 | Conversely, fumonisin B1, which selectively inhibits ceramide synthase and decreases de novo formation of ceramide, abolished the effects of palmitate on both PP2A and AMPK. |
| 605 | 17255104 | Inhibition of AMPK in parallel with increased PP2A activity was founded in C57BL/6J mice fed with high fat diet (HFD) rich in palmitate but not in mice fed with HFD rich in oleate. |
| 606 | 17255104 | Moreover, inhibition of PP2A with PP2A-specific siRNA but not scrambled siRNA reversed HFD-induced inhibition on the phosphorylation of AMPK-Thr(172) and endothelial nitric-oxide synthase (eNOS)-Ser(1177) in mice fed with high fat diets. |
| 607 | 17255104 | Taken together, we conclude that palmitate inhibits the phosphorylation of both AMPK and endothelial nitric-oxide synthase in endothelial cells via ceramide-dependent PP2A activation. |
| 608 | 18056794 | We conclude that subjects at risk for Type 2 diabetes have intrinsic differences in palmitate regulation of at least two enzymes (PP2A and glycogen synthase), contributing to abnormal insulin regulation of glucose metabolism. |
| 609 | 18077675 | Insulin dysfunction induces in vivo tau hyperphosphorylation through distinct mechanisms. |
| 610 | 18077675 | To investigate the possibility that insulin dysfunction might promote tau pathology, we induced insulin deficiency and caused DM in mice with streptozotocin (STZ). |
| 611 | 18077675 | No change in beta-amyloid (Abeta) precursor protein (APP), APP C-terminal fragments, or Abeta levels were observed in STZ-treated mice; however, cellular protein phosphatase 2A activity was significantly decreased. |
| 612 | 18077675 | Together, these data indicate that insulin dysfunction induced abnormal tau hyperphosphorylation through two distinct mechanisms: one was consequent to hypothermia; the other was temperature-independent, inherent to insulin depletion, and probably caused by inhibition of phosphatase activity. |
| 613 | 18486982 | Virus-induced over-expression of protein phosphatase 2A inhibits insulin signalling in chronic hepatitis C. |
| 614 | 18497878 | Vasoinhibins prevent retinal vasopermeability associated with diabetic retinopathy in rats via protein phosphatase 2A-dependent eNOS inactivation. |
| 615 | 18497878 | Vasoinhibins, a family of peptides derived from the protein hormone prolactin (and inclusive of the 16-kDa fragment of prolactin), antagonize the proangiogenic effects of VEGF, a primary mediator of retinal vasopermeability. |
| 616 | 18497878 | Inhibition by vasoinhibins was similar to that achieved following immunodepletion of VEGF from human diabetic retinopathy vitreous or blockage of NO synthesis, suggesting that vasoinhibins inhibit VEGF-induced NOS activation. |
| 617 | 18497878 | We further showed that vasoinhibins activate protein phosphatase 2A (PP2A), leading to eNOS dephosphorylation at Ser1179 and, thereby, eNOS inactivation. |
| 618 | 18497878 | Vasoinhibins prevent retinal vasopermeability associated with diabetic retinopathy in rats via protein phosphatase 2A-dependent eNOS inactivation. |
| 619 | 18497878 | Vasoinhibins, a family of peptides derived from the protein hormone prolactin (and inclusive of the 16-kDa fragment of prolactin), antagonize the proangiogenic effects of VEGF, a primary mediator of retinal vasopermeability. |
| 620 | 18497878 | Inhibition by vasoinhibins was similar to that achieved following immunodepletion of VEGF from human diabetic retinopathy vitreous or blockage of NO synthesis, suggesting that vasoinhibins inhibit VEGF-induced NOS activation. |
| 621 | 18497878 | We further showed that vasoinhibins activate protein phosphatase 2A (PP2A), leading to eNOS dephosphorylation at Ser1179 and, thereby, eNOS inactivation. |
| 622 | 18979206 | The forward reaction using ATP to generate phosphocreatine was reduced, while the reverse reaction using phosphocreatine to generate ATP was increased following dephosphorylation of immunoprecipitated M-CK with protein phosphatase 2A (PP2A) or PP2C. |
| 623 | 19249087 | A PP2A regulatory subunit regulates C. elegans insulin/IGF-1 signaling by modulating AKT-1 phosphorylation. |
| 624 | 19249087 | With striking conservation, mammalian B56beta regulates Akt phosphorylation at Thr 308 in 3T3-L1 adipocytes. |
| 625 | 19249087 | This study reveals a conserved role for the B56 regulatory subunit in regulating insulin signaling through AKT dephosphorylation, thereby having widespread implications in cancer and diabetes research. |
| 626 | 19690068 | Neither diabetes nor UCF-101 affected the expression of HtrA2/Omi and XIAP or caspase-3 activity. |
| 627 | 19690068 | UCF-101 significantly downregulated the AMPK-degrading enzymes PP2A and PP2C, the effect of which was mimicked by resveratrol. |
| 628 | 19798418 | The pathway involving serine/threonine-protein phosphatase (PP2A), an upstream regulator of lipid metabolism and insulin secretion, was found upregulated in early insulitis. |
| 629 | 19901535 | InAKTivation of insulin/IGF-1 signaling by dephosphorylation. |
| 630 | 19901535 | One such example is the C. elegans PP2A regulatory subunit PPTR-1 that negatively regulates the insulin/insulin-like growth factor signaling pathway to modulate longevity, dauer diapause, fat metabolism and stress resistance. |
| 631 | 19901535 | PPTR-1, as well as its mammalian homolog B56beta, specifically target the PP2A enzyme to AKT and mediate the dephosphorylation of this important kinase at a conserved threonine residue. |
| 632 | 19901535 | InAKTivation of insulin/IGF-1 signaling by dephosphorylation. |
| 633 | 19901535 | One such example is the C. elegans PP2A regulatory subunit PPTR-1 that negatively regulates the insulin/insulin-like growth factor signaling pathway to modulate longevity, dauer diapause, fat metabolism and stress resistance. |
| 634 | 19901535 | PPTR-1, as well as its mammalian homolog B56beta, specifically target the PP2A enzyme to AKT and mediate the dephosphorylation of this important kinase at a conserved threonine residue. |
| 635 | 20063116 | In addition, we observed that ceramide accumulation induced by NOE leads to a significant decrease in the levels of activated extracellular signal-regulated kinase (ERK); the inactivation of the ERK cascade in response to palmitate stimuli is induced by protein phosphatase 2A (PP2A) activity. |
| 636 | 20063116 | Based on these findings, we suggest that the aberrant accumulation of ceramide was caused by the inhibition of ceramide metabolism, which in turn leads to the inhibition of proinsulin gene expression; the inhibition of ERK cascades by PP2A serves as an important factor in the inhibitory effects of ceramide. |
| 637 | 20063116 | In addition, we observed that ceramide accumulation induced by NOE leads to a significant decrease in the levels of activated extracellular signal-regulated kinase (ERK); the inactivation of the ERK cascade in response to palmitate stimuli is induced by protein phosphatase 2A (PP2A) activity. |
| 638 | 20063116 | Based on these findings, we suggest that the aberrant accumulation of ceramide was caused by the inhibition of ceramide metabolism, which in turn leads to the inhibition of proinsulin gene expression; the inhibition of ERK cascades by PP2A serves as an important factor in the inhibitory effects of ceramide. |
| 639 | 20103773 | RACK1 mediated the glucose-inducible assembly of a complex containing IRE1alpha, RACK1, and protein phosphatase 2A (PP2A) to promote dephosphorylation of IRE1alpha by PP2A, thereby inhibiting glucose-stimulated IRE1alpha activation and attenuating IRE1alpha-dependent increases in insulin production. |
| 640 | 20161975 | Calyculins and related marine natural products as serine-threonine protein phosphatase PP1 and PP2A inhibitors and total syntheses of calyculin A, B, and C. |
| 641 | 20182580 | The serine/threonine protein kinase B (PKB, also known as Akt) constitutes an important node in diverse signaling cascades downstream of growth factor receptor tyrosine kinases. |
| 642 | 20182580 | This literature review details findings of those reports and others relevant to the regulation of Akt activation by its upstream kinases, with a focus on mammalian target of rapamycin complexes (mTORCs) and inactivation by PHLDA3 and the protein phosphatases PP2A and pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP). |
| 643 | 20182580 | Reports on ubiquitin-dependent Akt degradation, caspase-dependent cleavage, and the roles of molecular chaperone heat shock protein 90 (Hsp90) in the regulation of Akt stability are summarized. |
| 644 | 20182580 | The highlight will be on the role of "turn motif" phosphorylation and an isomerase, Pin1, in the regulation of Akt stability. |
| 645 | 20182580 | We also discuss issues related to the intricate mTORC2-AktmTORC1 loop and the contradictory regulation of Akt phosphorylation and stabilization of Akt by mTORC2. |
| 646 | 20551288 | Phosphorylation of the CREB-specific coactivator TORC2 at Ser(307) regulates its intracellular localization in COS-7 cells and in the mouse liver. |
| 647 | 20551288 | The CREB-specific coactivator TORC2 (also known as CRTC2) upregulates gluconeogenic gene expression in the liver. |
| 648 | 20551288 | Salt-inducible kinase (SIK) family enzymes inactivate TORC2 through phosphorylation and localize it in the cytoplasm. |
| 649 | 20551288 | Because the regulation of dephosphorylation at Ser(171) has not been fully clarified, we performed experiments with a range of doses of okadaic acid (OA), an inhibitor of PP2A/PP1, and with overexpression of various phosphatases and found that PP1 functions as an activator for TORC2, whereas PP2A acts as an inhibitor. |
| 650 | 20551288 | The Ser(307)-disrupted TORC2 was constitutively localized in the nucleus, but its coactivator activity was normally suppressed by SIK1 in COS-7 cells. |
| 651 | 20551288 | Levels of phosphorylation at Ser(171) and Ser(307) changed in response to fasting or fed conditions and insulin resistance of the mouse liver, which were modified by treatment with CsA/OA and by overexpression of PP1/PP2A/Cn. |
| 652 | 20551288 | These results suggest that multiple phosphorylation sites and their phosphatases may play important roles in regulating TORC2/CREB-mediated gluconeogenic programs in the liver. |
| 653 | 20551288 | Phosphorylation of the CREB-specific coactivator TORC2 at Ser(307) regulates its intracellular localization in COS-7 cells and in the mouse liver. |
| 654 | 20551288 | The CREB-specific coactivator TORC2 (also known as CRTC2) upregulates gluconeogenic gene expression in the liver. |
| 655 | 20551288 | Salt-inducible kinase (SIK) family enzymes inactivate TORC2 through phosphorylation and localize it in the cytoplasm. |
| 656 | 20551288 | Because the regulation of dephosphorylation at Ser(171) has not been fully clarified, we performed experiments with a range of doses of okadaic acid (OA), an inhibitor of PP2A/PP1, and with overexpression of various phosphatases and found that PP1 functions as an activator for TORC2, whereas PP2A acts as an inhibitor. |
| 657 | 20551288 | The Ser(307)-disrupted TORC2 was constitutively localized in the nucleus, but its coactivator activity was normally suppressed by SIK1 in COS-7 cells. |
| 658 | 20551288 | Levels of phosphorylation at Ser(171) and Ser(307) changed in response to fasting or fed conditions and insulin resistance of the mouse liver, which were modified by treatment with CsA/OA and by overexpression of PP1/PP2A/Cn. |
| 659 | 20551288 | These results suggest that multiple phosphorylation sites and their phosphatases may play important roles in regulating TORC2/CREB-mediated gluconeogenic programs in the liver. |
| 660 | 21281610 | GSK-3 phosphorylates microtube-associated protein tau at multiple sites, which can be antagonized by protein phosphatase-2A (PP-2A). |
| 661 | 21281610 | We observed that rat hippocampus tau was hyperphosphorylated at Ser(396)/Ser(404) (PHF-1 sites) in STZ-induced DM model, accompanied by lowered phosphorylation levels of Akt, GSK-3 and PP-2A. |
| 662 | 21281610 | Insulin administration restored the blood glucose level in DM rats but suppressed PP-2A activity, resulting in the PHF-1 sites of tau not being dephosphorylated. |
| 663 | 21281610 | These findings strongly suggest that STZ-induced hyperglycemia may cause disorder of Akt/GSK-3/PP-2A regulations in rat brain and further lead to abnormal phosphorylation of hippocampus tau. |
| 664 | 21281610 | GSK-3 phosphorylates microtube-associated protein tau at multiple sites, which can be antagonized by protein phosphatase-2A (PP-2A). |
| 665 | 21281610 | We observed that rat hippocampus tau was hyperphosphorylated at Ser(396)/Ser(404) (PHF-1 sites) in STZ-induced DM model, accompanied by lowered phosphorylation levels of Akt, GSK-3 and PP-2A. |
| 666 | 21281610 | Insulin administration restored the blood glucose level in DM rats but suppressed PP-2A activity, resulting in the PHF-1 sites of tau not being dephosphorylated. |
| 667 | 21281610 | These findings strongly suggest that STZ-induced hyperglycemia may cause disorder of Akt/GSK-3/PP-2A regulations in rat brain and further lead to abnormal phosphorylation of hippocampus tau. |
| 668 | 21281610 | GSK-3 phosphorylates microtube-associated protein tau at multiple sites, which can be antagonized by protein phosphatase-2A (PP-2A). |
| 669 | 21281610 | We observed that rat hippocampus tau was hyperphosphorylated at Ser(396)/Ser(404) (PHF-1 sites) in STZ-induced DM model, accompanied by lowered phosphorylation levels of Akt, GSK-3 and PP-2A. |
| 670 | 21281610 | Insulin administration restored the blood glucose level in DM rats but suppressed PP-2A activity, resulting in the PHF-1 sites of tau not being dephosphorylated. |
| 671 | 21281610 | These findings strongly suggest that STZ-induced hyperglycemia may cause disorder of Akt/GSK-3/PP-2A regulations in rat brain and further lead to abnormal phosphorylation of hippocampus tau. |
| 672 | 21281610 | GSK-3 phosphorylates microtube-associated protein tau at multiple sites, which can be antagonized by protein phosphatase-2A (PP-2A). |
| 673 | 21281610 | We observed that rat hippocampus tau was hyperphosphorylated at Ser(396)/Ser(404) (PHF-1 sites) in STZ-induced DM model, accompanied by lowered phosphorylation levels of Akt, GSK-3 and PP-2A. |
| 674 | 21281610 | Insulin administration restored the blood glucose level in DM rats but suppressed PP-2A activity, resulting in the PHF-1 sites of tau not being dephosphorylated. |
| 675 | 21281610 | These findings strongly suggest that STZ-induced hyperglycemia may cause disorder of Akt/GSK-3/PP-2A regulations in rat brain and further lead to abnormal phosphorylation of hippocampus tau. |
| 676 | 21427411 | AMP-activated protein kinase rescues the angiogenic functions of endothelial progenitor cells via manganese superoxide dismutase induction in type 1 diabetes. |
| 677 | 21427411 | AMP-activated protein kinase (AMPK) activation has been shown to induce MnSOD and suppress hyperglycemia-induced mitochondrial ROS production in endothelial cells. |
| 678 | 21427411 | We tested the hypothesis that AMPK activation rescues impaired EPC functions through MnSOD induction in type 1 diabetes. |
| 679 | 21427411 | These beneficial effects of AICAR on MnSOD and EPC functions were significantly attenuated by silencing MnSOD or AMPK antagonist compound C pretreatment. |
| 680 | 21427411 | Finally, the expression of protein phosphatase 2A, a key enzyme for AMPK dephosphorylation and inactivation, was increased in diabetic EPCs, and its inhibition by siRNA or okadaic acid reversed the deficient AMPK activation and MnSOD level in diabetic EPCs. |
| 681 | 21427411 | These findings demonstrate for the first time that AMPK activation rescues impaired EPC functions and suppresses mitochondrial superoxide by inducing MnSOD in type 1 diabetes. |
| 682 | 21497766 | Protein phosphatase 2A-SUR-6/B55 regulates centriole duplication in C. elegans by controlling the levels of centriole assembly factors. |
| 683 | 21497766 | In worms, flies, and humans, centriole assembly is dependent upon a key regulatory kinase (ZYG-1/Sak/Plk4) and its downstream effectors SAS-5 and SAS-6. |
| 684 | 21497766 | We find that the PP2A catalytic subunit LET-92, the scaffolding subunit PAA-1, and the B55 regulatory subunit SUR-6 function together to positively regulate centriole assembly. |
| 685 | 21497766 | In PP2A-SUR-6-depleted embryos, the levels of ZYG-1 and SAS-5 are reduced and the ZYG-1- and SAS-5-dependent recruitment of SAS-6 to the nascent centriole fails. |
| 686 | 21497766 | Protein phosphatase 2A-SUR-6/B55 regulates centriole duplication in C. elegans by controlling the levels of centriole assembly factors. |
| 687 | 21497766 | In worms, flies, and humans, centriole assembly is dependent upon a key regulatory kinase (ZYG-1/Sak/Plk4) and its downstream effectors SAS-5 and SAS-6. |
| 688 | 21497766 | We find that the PP2A catalytic subunit LET-92, the scaffolding subunit PAA-1, and the B55 regulatory subunit SUR-6 function together to positively regulate centriole assembly. |
| 689 | 21497766 | In PP2A-SUR-6-depleted embryos, the levels of ZYG-1 and SAS-5 are reduced and the ZYG-1- and SAS-5-dependent recruitment of SAS-6 to the nascent centriole fails. |
| 690 | 21497766 | Protein phosphatase 2A-SUR-6/B55 regulates centriole duplication in C. elegans by controlling the levels of centriole assembly factors. |
| 691 | 21497766 | In worms, flies, and humans, centriole assembly is dependent upon a key regulatory kinase (ZYG-1/Sak/Plk4) and its downstream effectors SAS-5 and SAS-6. |
| 692 | 21497766 | We find that the PP2A catalytic subunit LET-92, the scaffolding subunit PAA-1, and the B55 regulatory subunit SUR-6 function together to positively regulate centriole assembly. |
| 693 | 21497766 | In PP2A-SUR-6-depleted embryos, the levels of ZYG-1 and SAS-5 are reduced and the ZYG-1- and SAS-5-dependent recruitment of SAS-6 to the nascent centriole fails. |
| 694 | 21502318 | The beta-arrestin pathway-selective type 1A angiotensin receptor (AT1A) agonist [Sar1,Ile4,Ile8]angiotensin II regulates a robust G protein-independent signaling network. |
| 695 | 21502318 | The angiotensin II peptide analog [Sar(1),Ile(4),Ile(8)]AngII (SII) is a biased AT(1A) receptor agonist that stimulates receptor phosphorylation, β-arrestin recruitment, receptor internalization, and β-arrestin-dependent ERK1/2 activation without activating heterotrimeric G-proteins. |
| 696 | 21502318 | To determine the scope of G-protein-independent AT(1A) receptor signaling, we performed a gel-based phosphoproteomic analysis of AngII and SII-induced signaling in HEK cells stably expressing AT(1A) receptors. |
| 697 | 21502318 | MALDI-TOF/TOF mass fingerprinting was employed to identify 24 SII-sensitive phosphoprotein spots, of which three (two peptide inhibitors of protein phosphatase 2A (I1PP2A and I2PP2A) and prostaglandin E synthase 3 (PGES3)) were selected for validation and further study. |
| 698 | 21502318 | We found that phosphorylation of I2PP2A was associated with rapid and transient inhibition of a β-arrestin 2-associated pool of protein phosphatase 2A, leading to activation of Akt and increased phosphorylation of glycogen synthase kinase 3β in an arrestin signalsome complex. |
| 699 | 21502318 | The beta-arrestin pathway-selective type 1A angiotensin receptor (AT1A) agonist [Sar1,Ile4,Ile8]angiotensin II regulates a robust G protein-independent signaling network. |
| 700 | 21502318 | The angiotensin II peptide analog [Sar(1),Ile(4),Ile(8)]AngII (SII) is a biased AT(1A) receptor agonist that stimulates receptor phosphorylation, β-arrestin recruitment, receptor internalization, and β-arrestin-dependent ERK1/2 activation without activating heterotrimeric G-proteins. |
| 701 | 21502318 | To determine the scope of G-protein-independent AT(1A) receptor signaling, we performed a gel-based phosphoproteomic analysis of AngII and SII-induced signaling in HEK cells stably expressing AT(1A) receptors. |
| 702 | 21502318 | MALDI-TOF/TOF mass fingerprinting was employed to identify 24 SII-sensitive phosphoprotein spots, of which three (two peptide inhibitors of protein phosphatase 2A (I1PP2A and I2PP2A) and prostaglandin E synthase 3 (PGES3)) were selected for validation and further study. |
| 703 | 21502318 | We found that phosphorylation of I2PP2A was associated with rapid and transient inhibition of a β-arrestin 2-associated pool of protein phosphatase 2A, leading to activation of Akt and increased phosphorylation of glycogen synthase kinase 3β in an arrestin signalsome complex. |
| 704 | 22031698 | Here we describe that targeting Akt kinase to the cell membrane markedly reduced sensitivity of phosphorylated Akt to dephosphorylation by protein phosphatase 2A. |
| 705 | 22087313 | Free fatty acid-induced PP2A hyperactivity selectively impairs hepatic insulin action on glucose metabolism. |
| 706 | 22087313 | While insulin-receptor phosphorylation was unaffected, activation of Akt and inactivation of the downstream targets Glycogen synthase kinase 3α (Gsk3α and Forkhead box O1 (FoxO1) was inhibited in palmitate-exposed cells. |
| 707 | 22087313 | Accordingly, dose-response curves for insulin-mediated suppression of the FoxO1-induced gluconeogenic genes and for de novo glucose production were right shifted, and insulin-stimulated glucose oxidation and glycogen synthesis were impaired. |
| 708 | 22087313 | The activity of the Akt-inactivating Protein Phosphatase 2A (PP2A) was increased in the insulin-resistant cells. |
| 709 | 22087313 | Furthermore, inhibition of PP2A by specific inhibitors increased insulin-stimulated activation of Akt and phosphorylation of FoxO1 and Gsk3α. |
| 710 | 22087313 | Finally, PP2A mRNA levels were increased in liver, muscle and adipose tissue, while PP2A activity was increased in liver and muscle tissue in insulin-resistant ZDF rats. |
| 711 | 22087313 | In conclusion, our findings indicate that FFAs may cause a selective impairment of insulin action upon hepatic glucose metabolism by increasing PP2A activity. |
| 712 | 22087313 | Free fatty acid-induced PP2A hyperactivity selectively impairs hepatic insulin action on glucose metabolism. |
| 713 | 22087313 | While insulin-receptor phosphorylation was unaffected, activation of Akt and inactivation of the downstream targets Glycogen synthase kinase 3α (Gsk3α and Forkhead box O1 (FoxO1) was inhibited in palmitate-exposed cells. |
| 714 | 22087313 | Accordingly, dose-response curves for insulin-mediated suppression of the FoxO1-induced gluconeogenic genes and for de novo glucose production were right shifted, and insulin-stimulated glucose oxidation and glycogen synthesis were impaired. |
| 715 | 22087313 | The activity of the Akt-inactivating Protein Phosphatase 2A (PP2A) was increased in the insulin-resistant cells. |
| 716 | 22087313 | Furthermore, inhibition of PP2A by specific inhibitors increased insulin-stimulated activation of Akt and phosphorylation of FoxO1 and Gsk3α. |
| 717 | 22087313 | Finally, PP2A mRNA levels were increased in liver, muscle and adipose tissue, while PP2A activity was increased in liver and muscle tissue in insulin-resistant ZDF rats. |
| 718 | 22087313 | In conclusion, our findings indicate that FFAs may cause a selective impairment of insulin action upon hepatic glucose metabolism by increasing PP2A activity. |
| 719 | 22087313 | Free fatty acid-induced PP2A hyperactivity selectively impairs hepatic insulin action on glucose metabolism. |
| 720 | 22087313 | While insulin-receptor phosphorylation was unaffected, activation of Akt and inactivation of the downstream targets Glycogen synthase kinase 3α (Gsk3α and Forkhead box O1 (FoxO1) was inhibited in palmitate-exposed cells. |
| 721 | 22087313 | Accordingly, dose-response curves for insulin-mediated suppression of the FoxO1-induced gluconeogenic genes and for de novo glucose production were right shifted, and insulin-stimulated glucose oxidation and glycogen synthesis were impaired. |
| 722 | 22087313 | The activity of the Akt-inactivating Protein Phosphatase 2A (PP2A) was increased in the insulin-resistant cells. |
| 723 | 22087313 | Furthermore, inhibition of PP2A by specific inhibitors increased insulin-stimulated activation of Akt and phosphorylation of FoxO1 and Gsk3α. |
| 724 | 22087313 | Finally, PP2A mRNA levels were increased in liver, muscle and adipose tissue, while PP2A activity was increased in liver and muscle tissue in insulin-resistant ZDF rats. |
| 725 | 22087313 | In conclusion, our findings indicate that FFAs may cause a selective impairment of insulin action upon hepatic glucose metabolism by increasing PP2A activity. |
| 726 | 22087313 | Free fatty acid-induced PP2A hyperactivity selectively impairs hepatic insulin action on glucose metabolism. |
| 727 | 22087313 | While insulin-receptor phosphorylation was unaffected, activation of Akt and inactivation of the downstream targets Glycogen synthase kinase 3α (Gsk3α and Forkhead box O1 (FoxO1) was inhibited in palmitate-exposed cells. |
| 728 | 22087313 | Accordingly, dose-response curves for insulin-mediated suppression of the FoxO1-induced gluconeogenic genes and for de novo glucose production were right shifted, and insulin-stimulated glucose oxidation and glycogen synthesis were impaired. |
| 729 | 22087313 | The activity of the Akt-inactivating Protein Phosphatase 2A (PP2A) was increased in the insulin-resistant cells. |
| 730 | 22087313 | Furthermore, inhibition of PP2A by specific inhibitors increased insulin-stimulated activation of Akt and phosphorylation of FoxO1 and Gsk3α. |
| 731 | 22087313 | Finally, PP2A mRNA levels were increased in liver, muscle and adipose tissue, while PP2A activity was increased in liver and muscle tissue in insulin-resistant ZDF rats. |
| 732 | 22087313 | In conclusion, our findings indicate that FFAs may cause a selective impairment of insulin action upon hepatic glucose metabolism by increasing PP2A activity. |
| 733 | 22087313 | Free fatty acid-induced PP2A hyperactivity selectively impairs hepatic insulin action on glucose metabolism. |
| 734 | 22087313 | While insulin-receptor phosphorylation was unaffected, activation of Akt and inactivation of the downstream targets Glycogen synthase kinase 3α (Gsk3α and Forkhead box O1 (FoxO1) was inhibited in palmitate-exposed cells. |
| 735 | 22087313 | Accordingly, dose-response curves for insulin-mediated suppression of the FoxO1-induced gluconeogenic genes and for de novo glucose production were right shifted, and insulin-stimulated glucose oxidation and glycogen synthesis were impaired. |
| 736 | 22087313 | The activity of the Akt-inactivating Protein Phosphatase 2A (PP2A) was increased in the insulin-resistant cells. |
| 737 | 22087313 | Furthermore, inhibition of PP2A by specific inhibitors increased insulin-stimulated activation of Akt and phosphorylation of FoxO1 and Gsk3α. |
| 738 | 22087313 | Finally, PP2A mRNA levels were increased in liver, muscle and adipose tissue, while PP2A activity was increased in liver and muscle tissue in insulin-resistant ZDF rats. |
| 739 | 22087313 | In conclusion, our findings indicate that FFAs may cause a selective impairment of insulin action upon hepatic glucose metabolism by increasing PP2A activity. |
| 740 | 22509362 | Deregulation of CREB signaling pathway induced by chronic hyperglycemia downregulates NeuroD transcription. |
| 741 | 22509362 | CREB mediates the transcriptional effects of glucose and incretin hormones in insulin-target cells and insulin-producing β-cells. |
| 742 | 22509362 | Here, we show that β-cell dysfunctions occurring in chronic hyperglycemia are not caused by simple inhibition of CREB activity but rather by the persistent activation of CREB due to decreases in protein phophatase PP2A. |
| 743 | 22509362 | The excessively produced ICER was sufficient to repress the transcription of NeuroD, insulin, and SUR1 genes. |
| 744 | 22509362 | Importantly, overexpression of PP2A reversed the adverse effects of chronic hyperglycemia and successfully restored the transient activation of CREB and ICER. |
| 745 | 22509362 | Conversely, depletion of PP2A with siRNA was sufficient to disrupt the negative feedback regulation of CREB and induce hyperglycemic phenotypes even under low glucose conditions. |
| 746 | 22509362 | Our findings suggest that the failure of the negative feedback regulation of CREB is the primary cause for β-cell dysfunctions under conditions of pathogenic hyperglycemia, and PP2A can be a novel target for future therapies aiming to protect β-cells mass in the late transitional phase of non-insulin dependent type 2 diabetes (NIDDM). |
| 747 | 22509362 | Deregulation of CREB signaling pathway induced by chronic hyperglycemia downregulates NeuroD transcription. |
| 748 | 22509362 | CREB mediates the transcriptional effects of glucose and incretin hormones in insulin-target cells and insulin-producing β-cells. |
| 749 | 22509362 | Here, we show that β-cell dysfunctions occurring in chronic hyperglycemia are not caused by simple inhibition of CREB activity but rather by the persistent activation of CREB due to decreases in protein phophatase PP2A. |
| 750 | 22509362 | The excessively produced ICER was sufficient to repress the transcription of NeuroD, insulin, and SUR1 genes. |
| 751 | 22509362 | Importantly, overexpression of PP2A reversed the adverse effects of chronic hyperglycemia and successfully restored the transient activation of CREB and ICER. |
| 752 | 22509362 | Conversely, depletion of PP2A with siRNA was sufficient to disrupt the negative feedback regulation of CREB and induce hyperglycemic phenotypes even under low glucose conditions. |
| 753 | 22509362 | Our findings suggest that the failure of the negative feedback regulation of CREB is the primary cause for β-cell dysfunctions under conditions of pathogenic hyperglycemia, and PP2A can be a novel target for future therapies aiming to protect β-cells mass in the late transitional phase of non-insulin dependent type 2 diabetes (NIDDM). |
| 754 | 22509362 | Deregulation of CREB signaling pathway induced by chronic hyperglycemia downregulates NeuroD transcription. |
| 755 | 22509362 | CREB mediates the transcriptional effects of glucose and incretin hormones in insulin-target cells and insulin-producing β-cells. |
| 756 | 22509362 | Here, we show that β-cell dysfunctions occurring in chronic hyperglycemia are not caused by simple inhibition of CREB activity but rather by the persistent activation of CREB due to decreases in protein phophatase PP2A. |
| 757 | 22509362 | The excessively produced ICER was sufficient to repress the transcription of NeuroD, insulin, and SUR1 genes. |
| 758 | 22509362 | Importantly, overexpression of PP2A reversed the adverse effects of chronic hyperglycemia and successfully restored the transient activation of CREB and ICER. |
| 759 | 22509362 | Conversely, depletion of PP2A with siRNA was sufficient to disrupt the negative feedback regulation of CREB and induce hyperglycemic phenotypes even under low glucose conditions. |
| 760 | 22509362 | Our findings suggest that the failure of the negative feedback regulation of CREB is the primary cause for β-cell dysfunctions under conditions of pathogenic hyperglycemia, and PP2A can be a novel target for future therapies aiming to protect β-cells mass in the late transitional phase of non-insulin dependent type 2 diabetes (NIDDM). |
| 761 | 22509362 | Deregulation of CREB signaling pathway induced by chronic hyperglycemia downregulates NeuroD transcription. |
| 762 | 22509362 | CREB mediates the transcriptional effects of glucose and incretin hormones in insulin-target cells and insulin-producing β-cells. |
| 763 | 22509362 | Here, we show that β-cell dysfunctions occurring in chronic hyperglycemia are not caused by simple inhibition of CREB activity but rather by the persistent activation of CREB due to decreases in protein phophatase PP2A. |
| 764 | 22509362 | The excessively produced ICER was sufficient to repress the transcription of NeuroD, insulin, and SUR1 genes. |
| 765 | 22509362 | Importantly, overexpression of PP2A reversed the adverse effects of chronic hyperglycemia and successfully restored the transient activation of CREB and ICER. |
| 766 | 22509362 | Conversely, depletion of PP2A with siRNA was sufficient to disrupt the negative feedback regulation of CREB and induce hyperglycemic phenotypes even under low glucose conditions. |
| 767 | 22509362 | Our findings suggest that the failure of the negative feedback regulation of CREB is the primary cause for β-cell dysfunctions under conditions of pathogenic hyperglycemia, and PP2A can be a novel target for future therapies aiming to protect β-cells mass in the late transitional phase of non-insulin dependent type 2 diabetes (NIDDM). |
| 768 | 22586587 | Studies in endothelial cells reveal that de novo ceramide biosynthesis induced protein phosphatase 2A (PP2A) association directly with the endothelial nitric oxide synthase (eNOS)/Akt/Hsp90 complex that was concurrent with decreased basal and agonist-stimulated eNOS phosphorylation. |
| 769 | 22586587 | PP2A attenuates eNOS phosphorylation by preventing phosphorylation of the pool of Akt that colocalizes with eNOS and by dephosphorylating eNOS. |
| 770 | 22586587 | We conclude that ceramide mediates obesity-related vascular dysfunction by a mechanism that involves PP2A-mediated disruption of the eNOS/Akt/Hsp90 signaling complex. |
| 771 | 22586587 | Studies in endothelial cells reveal that de novo ceramide biosynthesis induced protein phosphatase 2A (PP2A) association directly with the endothelial nitric oxide synthase (eNOS)/Akt/Hsp90 complex that was concurrent with decreased basal and agonist-stimulated eNOS phosphorylation. |
| 772 | 22586587 | PP2A attenuates eNOS phosphorylation by preventing phosphorylation of the pool of Akt that colocalizes with eNOS and by dephosphorylating eNOS. |
| 773 | 22586587 | We conclude that ceramide mediates obesity-related vascular dysfunction by a mechanism that involves PP2A-mediated disruption of the eNOS/Akt/Hsp90 signaling complex. |
| 774 | 22586587 | Studies in endothelial cells reveal that de novo ceramide biosynthesis induced protein phosphatase 2A (PP2A) association directly with the endothelial nitric oxide synthase (eNOS)/Akt/Hsp90 complex that was concurrent with decreased basal and agonist-stimulated eNOS phosphorylation. |
| 775 | 22586587 | PP2A attenuates eNOS phosphorylation by preventing phosphorylation of the pool of Akt that colocalizes with eNOS and by dephosphorylating eNOS. |
| 776 | 22586587 | We conclude that ceramide mediates obesity-related vascular dysfunction by a mechanism that involves PP2A-mediated disruption of the eNOS/Akt/Hsp90 signaling complex. |
| 777 | 22641604 | Phosphoinositide (PI) phosphatases such as the SH2 domain-containing inositol 5-phosphatases 1/2 (SHIP1 and 2) are important signalling enzymes in human physiopathology. |
| 778 | 22641604 | Since a subunit of the Ser/Thr phosphatase PP2A has been shown to interact with SHIP2, a putative mechanism for reversing SHIP2 Ser/Thr phosphorylation can be anticipated. |
| 779 | 22641604 | This mechanism may be more broadly involved in regulating PI signalling in the case of synaptojanin1 or the phosphatase, tensin homolog, deleted on chromosome TEN. |
| 780 | 22886408 | Pravastatin normalizes ET-1-induced contraction in the aorta of type 2 diabetic OLETF rats by suppressing the KSR1/ERK complex. |
| 781 | 22886408 | Both immunoblot analysis and immunoprecipitation assays were used to examine Src, protein phosphatase (PP)2A, kinase suppressor of Ras (KSR)1, and ERK signaling pathway protein levels and activities. |
| 782 | 22886408 | In endothelium-denuded aortas isolated from OLETF rats at the chronic stage of diabetes (56-60 wk) (vs. those from age-matched LETO rats), we found the following: 1) ET-1-induced contraction was enhanced, 2) ERK1/2 phosphorylation was increased, 3) phosphorylations of KSR1 and PP2A were reduced (i.e., enhancement of the kinase active state), 4) ERK1/2-KSR1 complexes were increased, and 5) Src tyrosine kinase activity was diminished. |
| 783 | 22886408 | Endothelium-denuded aortas isolated from OLETF rats treated with pravastatin (10 mg/kg po, daily for 4 wk) exhibited normalized ET-1-induced contractions and suppressed ET-1-stimulated ERK phosphorylation, with the associated phosphorylated KSR1 and phosphorylated PP2A levels being increased toward normal levels. |
| 784 | 22886408 | These results suggest that in type 2 diabetic rats, pravastatin normalizes ET-1-induced contraction in aortic smooth muscle via a suppression of PP2A/KSR1/ERK activities after an enhancement of Src kinase activity. |
| 785 | 22886408 | Pravastatin normalizes ET-1-induced contraction in the aorta of type 2 diabetic OLETF rats by suppressing the KSR1/ERK complex. |
| 786 | 22886408 | Both immunoblot analysis and immunoprecipitation assays were used to examine Src, protein phosphatase (PP)2A, kinase suppressor of Ras (KSR)1, and ERK signaling pathway protein levels and activities. |
| 787 | 22886408 | In endothelium-denuded aortas isolated from OLETF rats at the chronic stage of diabetes (56-60 wk) (vs. those from age-matched LETO rats), we found the following: 1) ET-1-induced contraction was enhanced, 2) ERK1/2 phosphorylation was increased, 3) phosphorylations of KSR1 and PP2A were reduced (i.e., enhancement of the kinase active state), 4) ERK1/2-KSR1 complexes were increased, and 5) Src tyrosine kinase activity was diminished. |
| 788 | 22886408 | Endothelium-denuded aortas isolated from OLETF rats treated with pravastatin (10 mg/kg po, daily for 4 wk) exhibited normalized ET-1-induced contractions and suppressed ET-1-stimulated ERK phosphorylation, with the associated phosphorylated KSR1 and phosphorylated PP2A levels being increased toward normal levels. |
| 789 | 22886408 | These results suggest that in type 2 diabetic rats, pravastatin normalizes ET-1-induced contraction in aortic smooth muscle via a suppression of PP2A/KSR1/ERK activities after an enhancement of Src kinase activity. |
| 790 | 22886408 | Pravastatin normalizes ET-1-induced contraction in the aorta of type 2 diabetic OLETF rats by suppressing the KSR1/ERK complex. |
| 791 | 22886408 | Both immunoblot analysis and immunoprecipitation assays were used to examine Src, protein phosphatase (PP)2A, kinase suppressor of Ras (KSR)1, and ERK signaling pathway protein levels and activities. |
| 792 | 22886408 | In endothelium-denuded aortas isolated from OLETF rats at the chronic stage of diabetes (56-60 wk) (vs. those from age-matched LETO rats), we found the following: 1) ET-1-induced contraction was enhanced, 2) ERK1/2 phosphorylation was increased, 3) phosphorylations of KSR1 and PP2A were reduced (i.e., enhancement of the kinase active state), 4) ERK1/2-KSR1 complexes were increased, and 5) Src tyrosine kinase activity was diminished. |
| 793 | 22886408 | Endothelium-denuded aortas isolated from OLETF rats treated with pravastatin (10 mg/kg po, daily for 4 wk) exhibited normalized ET-1-induced contractions and suppressed ET-1-stimulated ERK phosphorylation, with the associated phosphorylated KSR1 and phosphorylated PP2A levels being increased toward normal levels. |
| 794 | 22886408 | These results suggest that in type 2 diabetic rats, pravastatin normalizes ET-1-induced contraction in aortic smooth muscle via a suppression of PP2A/KSR1/ERK activities after an enhancement of Src kinase activity. |
| 795 | 22961084 | Our data indicate that insulin dysfunction in NOD mice leads to AD-like τ hyperphosphorylation in the brain, with molecular mechanisms likely involving a deregulation of PP2A. |
| 796 | 23463119 | HCV core protein was shown to stimulate suppressor of cytokine signaling, resulting in ubiquitination and degradation of tyrosine kinase phosphorylated insulin receptor substrates (IRS1/2) in proteasomes. |
| 797 | 23463119 | HCV-nonstructural protein could increase protein phosphatase 2A which has been shown to inactivate the key enzyme Akt by dephosphorylating it. |
| 798 | 23463119 | Insulin signaling defects in hepatic IRS-1 tyrosine phosphorylation and PI3-kinase association/activation may contribute to IR, which leads to the development of T2D in patients with HCV infection. |
| 799 | 23463119 | PPARα upregulates glycerol-3-phosphate dehydrogenase, glycerol kinase, and glycerol transport proteins, which allows for glucose synthesis during fasting states. |
| 800 | 23463119 | It is speculated that TNF-alpha plays a major role in the pathogenesis of IR through lowering IRS1/2. |
| 801 | 23463119 | Furthermore, HCV infection- triggered ER stress could lead to the activation of PP2A, which inhibits both Akt and the AMP-activated kinase, the regulators of gluconeogenesis. |
| 802 | 23463119 | HCV core protein was shown to stimulate suppressor of cytokine signaling, resulting in ubiquitination and degradation of tyrosine kinase phosphorylated insulin receptor substrates (IRS1/2) in proteasomes. |
| 803 | 23463119 | HCV-nonstructural protein could increase protein phosphatase 2A which has been shown to inactivate the key enzyme Akt by dephosphorylating it. |
| 804 | 23463119 | Insulin signaling defects in hepatic IRS-1 tyrosine phosphorylation and PI3-kinase association/activation may contribute to IR, which leads to the development of T2D in patients with HCV infection. |
| 805 | 23463119 | PPARα upregulates glycerol-3-phosphate dehydrogenase, glycerol kinase, and glycerol transport proteins, which allows for glucose synthesis during fasting states. |
| 806 | 23463119 | It is speculated that TNF-alpha plays a major role in the pathogenesis of IR through lowering IRS1/2. |
| 807 | 23463119 | Furthermore, HCV infection- triggered ER stress could lead to the activation of PP2A, which inhibits both Akt and the AMP-activated kinase, the regulators of gluconeogenesis. |
| 808 | 23581463 | Troglitazone, a thiazolidinedione, decreases tau phosphorylation through the inhibition of cyclin-dependent kinase 5 activity in SH-SY5Y neuroblastoma cells and primary neurons. |
| 809 | 23581463 | Here, we investigated whether and how troglitazone, a parent TZD drug, inhibits tau phosphorylation.Treatment with troglitazone decreased tau-Thr231 phosphorylation and p35, the specific activator of cyclin-dependent kinase 5 (CDK5), in a dose- and time-dependent manner. |
| 810 | 23581463 | Troglitazone also decreased CDK5 enzymatic activity, and ectopic expression of p25, the cleaved and more active form of p35, restored the troglitazone-induced decrease in tau-Thr231 phosphorylation. |
| 811 | 23581463 | Treatment with various inhibitors revealed that troglitazone-induced inhibitions of tau-Thr231 phosphorylation and p35 expression were not mediated by glycogen synthase kinase 3b, protein kinase A, and protein phosphatase 2A signaling pathways.Finally, we also found that the same observed inhibitory effects of troglitazone hold true for the use of primary cortical neurons. |
| 812 | 23581463 | Taken together, we demonstrated that TZDs repressed tau-Thr231 phosphorylation via the inhibition of CDK5 activity, which was mediated by the proteasomal degradation of p35 and a PPARc-independent signaling pathway. |
| 813 | 23640887 | In acidic conditions such as generated by brain ischemia and hypoxia, especially in association with hyperglycemia as in diabetes, I2(PP2A) is cleaved by asparaginyl endopeptidase at Asn-175 into the N-terminal fragment (I2NTF) and the C-terminal fragment (I2CTF). |
| 814 | 23640887 | Here we show that the level of activated asparaginyl endopeptidase is significantly increased, and this enzyme and I2(PP2A) translocate, respectively, from neuronal lysosomes and nucleus to the cytoplasm where they interact and are associated with hyperphosphorylated Tau in Alzheimer disease brain. |
| 815 | 23640887 | Asparaginyl endopeptidase from Alzheimer disease brain could cleave GST-I2(PP2A), except when I2(PP2A) was mutated at the cleavage site Asn-175 to Gln. |
| 816 | 23640887 | Finally, an induction of acidosis by treatment with kainic acid or pH 6.0 medium activated asparaginyl endopeptidase and consequently produced the cleavage of I2(PP2A), inhibition of protein phosphatase 2A, and hyperphosphorylation of Tau, and the knockdown of asparaginyl endopeptidase with siRNA abolished this pathway in SH-SY5Y cells. |
| 817 | 23640887 | These findings suggest the involvement of brain acidosis in the etiopathogenesis of Alzheimer disease, and asparaginyl endopeptidase-I2(PP2A)-protein phosphatase 2A-Tau hyperphosphorylation pathway as a therapeutic target. |
| 818 | 23640887 | In acidic conditions such as generated by brain ischemia and hypoxia, especially in association with hyperglycemia as in diabetes, I2(PP2A) is cleaved by asparaginyl endopeptidase at Asn-175 into the N-terminal fragment (I2NTF) and the C-terminal fragment (I2CTF). |
| 819 | 23640887 | Here we show that the level of activated asparaginyl endopeptidase is significantly increased, and this enzyme and I2(PP2A) translocate, respectively, from neuronal lysosomes and nucleus to the cytoplasm where they interact and are associated with hyperphosphorylated Tau in Alzheimer disease brain. |
| 820 | 23640887 | Asparaginyl endopeptidase from Alzheimer disease brain could cleave GST-I2(PP2A), except when I2(PP2A) was mutated at the cleavage site Asn-175 to Gln. |
| 821 | 23640887 | Finally, an induction of acidosis by treatment with kainic acid or pH 6.0 medium activated asparaginyl endopeptidase and consequently produced the cleavage of I2(PP2A), inhibition of protein phosphatase 2A, and hyperphosphorylation of Tau, and the knockdown of asparaginyl endopeptidase with siRNA abolished this pathway in SH-SY5Y cells. |
| 822 | 23640887 | These findings suggest the involvement of brain acidosis in the etiopathogenesis of Alzheimer disease, and asparaginyl endopeptidase-I2(PP2A)-protein phosphatase 2A-Tau hyperphosphorylation pathway as a therapeutic target. |
| 823 | 23640887 | In acidic conditions such as generated by brain ischemia and hypoxia, especially in association with hyperglycemia as in diabetes, I2(PP2A) is cleaved by asparaginyl endopeptidase at Asn-175 into the N-terminal fragment (I2NTF) and the C-terminal fragment (I2CTF). |
| 824 | 23640887 | Here we show that the level of activated asparaginyl endopeptidase is significantly increased, and this enzyme and I2(PP2A) translocate, respectively, from neuronal lysosomes and nucleus to the cytoplasm where they interact and are associated with hyperphosphorylated Tau in Alzheimer disease brain. |
| 825 | 23640887 | Asparaginyl endopeptidase from Alzheimer disease brain could cleave GST-I2(PP2A), except when I2(PP2A) was mutated at the cleavage site Asn-175 to Gln. |
| 826 | 23640887 | Finally, an induction of acidosis by treatment with kainic acid or pH 6.0 medium activated asparaginyl endopeptidase and consequently produced the cleavage of I2(PP2A), inhibition of protein phosphatase 2A, and hyperphosphorylation of Tau, and the knockdown of asparaginyl endopeptidase with siRNA abolished this pathway in SH-SY5Y cells. |
| 827 | 23640887 | These findings suggest the involvement of brain acidosis in the etiopathogenesis of Alzheimer disease, and asparaginyl endopeptidase-I2(PP2A)-protein phosphatase 2A-Tau hyperphosphorylation pathway as a therapeutic target. |
| 828 | 23640887 | In acidic conditions such as generated by brain ischemia and hypoxia, especially in association with hyperglycemia as in diabetes, I2(PP2A) is cleaved by asparaginyl endopeptidase at Asn-175 into the N-terminal fragment (I2NTF) and the C-terminal fragment (I2CTF). |
| 829 | 23640887 | Here we show that the level of activated asparaginyl endopeptidase is significantly increased, and this enzyme and I2(PP2A) translocate, respectively, from neuronal lysosomes and nucleus to the cytoplasm where they interact and are associated with hyperphosphorylated Tau in Alzheimer disease brain. |
| 830 | 23640887 | Asparaginyl endopeptidase from Alzheimer disease brain could cleave GST-I2(PP2A), except when I2(PP2A) was mutated at the cleavage site Asn-175 to Gln. |
| 831 | 23640887 | Finally, an induction of acidosis by treatment with kainic acid or pH 6.0 medium activated asparaginyl endopeptidase and consequently produced the cleavage of I2(PP2A), inhibition of protein phosphatase 2A, and hyperphosphorylation of Tau, and the knockdown of asparaginyl endopeptidase with siRNA abolished this pathway in SH-SY5Y cells. |
| 832 | 23640887 | These findings suggest the involvement of brain acidosis in the etiopathogenesis of Alzheimer disease, and asparaginyl endopeptidase-I2(PP2A)-protein phosphatase 2A-Tau hyperphosphorylation pathway as a therapeutic target. |
| 833 | 23640887 | In acidic conditions such as generated by brain ischemia and hypoxia, especially in association with hyperglycemia as in diabetes, I2(PP2A) is cleaved by asparaginyl endopeptidase at Asn-175 into the N-terminal fragment (I2NTF) and the C-terminal fragment (I2CTF). |
| 834 | 23640887 | Here we show that the level of activated asparaginyl endopeptidase is significantly increased, and this enzyme and I2(PP2A) translocate, respectively, from neuronal lysosomes and nucleus to the cytoplasm where they interact and are associated with hyperphosphorylated Tau in Alzheimer disease brain. |
| 835 | 23640887 | Asparaginyl endopeptidase from Alzheimer disease brain could cleave GST-I2(PP2A), except when I2(PP2A) was mutated at the cleavage site Asn-175 to Gln. |
| 836 | 23640887 | Finally, an induction of acidosis by treatment with kainic acid or pH 6.0 medium activated asparaginyl endopeptidase and consequently produced the cleavage of I2(PP2A), inhibition of protein phosphatase 2A, and hyperphosphorylation of Tau, and the knockdown of asparaginyl endopeptidase with siRNA abolished this pathway in SH-SY5Y cells. |
| 837 | 23640887 | These findings suggest the involvement of brain acidosis in the etiopathogenesis of Alzheimer disease, and asparaginyl endopeptidase-I2(PP2A)-protein phosphatase 2A-Tau hyperphosphorylation pathway as a therapeutic target. |