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Gene Information
Gene symbol: SRC
Gene name: v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian)
HGNC ID: 11283
Synonyms: ASV, c-src
Related Genes
Related Sentences
| # | PMID | Sentence |
| 1 | 1372896 | RNAs corresponding to known insulin-responsive genes such as c-fos, c-myc, c-Ha-ras, and c-src displayed rapid and transient 2-4-fold increases between 30 and 60 min as detected by either Northern analysis or the multiple S1 nuclease protection assay. |
| 2 | 1372896 | In addition, RNA levels for the insulin receptor, Glut-4, Glut-3, and c-jun were apparently unaffected by exposure of the cells to insulin. |
| 3 | 7504175 | Pleiotropic insulin signals are engaged by multisite phosphorylation of IRS-1. |
| 4 | 7504175 | Tyrosine-phosphorylated IRS-1 binds specifically to various cellular proteins containing Src homology 2 (SH2) domains (SH2 proteins). |
| 5 | 7504175 | We identified some of the tyrosine residues of IRS-1 that undergo insulin-stimulated phosphorylation by the purified insulin receptor and in intact cells during insulin stimulation. |
| 6 | 7504175 | These results extend the notion that IRS-1 is a multisite docking protein that engages various downstream regulatory elements during insulin signal transmission. |
| 7 | 7520528 | Second, we demonstrate a direct binding between purified SH2 and SH3 domains of Fyn and Lck Src family kinases. |
| 8 | 7520528 | Heterologous binding between SH2 and SH3 domains of closely related members of the Src family, namely, Fyn, Lck, and Src, was also observed. |
| 9 | 7520528 | In contrast, Grb2, Crk, Abl, p85 phosphatidylinositol 3-kinase, and GTPase-activating protein SH2 domains showed lower or no binding to Fyn or Lck SH3 domains. |
| 10 | 7520528 | SH3-SH2 binding was observed in the presence of proline-rich peptides or when a point mutation (W119K) was introduced in the putative ligand-binding pouch of the Fyn SH3 domain, although these treatments completely abolished the binding to p85 phosphatidylinositol 3-kinase and other SH3-specific polypeptides. |
| 11 | 7520528 | Second, we demonstrate a direct binding between purified SH2 and SH3 domains of Fyn and Lck Src family kinases. |
| 12 | 7520528 | Heterologous binding between SH2 and SH3 domains of closely related members of the Src family, namely, Fyn, Lck, and Src, was also observed. |
| 13 | 7520528 | In contrast, Grb2, Crk, Abl, p85 phosphatidylinositol 3-kinase, and GTPase-activating protein SH2 domains showed lower or no binding to Fyn or Lck SH3 domains. |
| 14 | 7520528 | SH3-SH2 binding was observed in the presence of proline-rich peptides or when a point mutation (W119K) was introduced in the putative ligand-binding pouch of the Fyn SH3 domain, although these treatments completely abolished the binding to p85 phosphatidylinositol 3-kinase and other SH3-specific polypeptides. |
| 15 | 7961682 | Interactive roles of Ras, insulin receptor substrate-1, and proteins with Src homology-2 domains in insulin signaling in Xenopus oocytes. |
| 16 | 7961682 | Insulin receptor substrate-1 (IRS-1) serves as the major immediate substrate of insulin/insulin-like growth factor (IGF)-1 receptors and following tyrosine phosphorylation binds to specific Src homology-2 (SH2) domain-containing proteins including the p85 subunit of phosphatidylinositol (PI) 3-kinase and GRB2, a molecule believed to link IRS-1 to the Ras pathway. |
| 17 | 7961682 | To investigate how these SH2-containing signaling molecules interact to regulate insulin/IGF-1 action, IRS-1, glutathione S-transferase (GST)-SH2 domain fusion proteins and Ras proteins were microinjected into Xenopus oocytes. |
| 18 | 7961682 | We found that pleiotropic insulin actions are mediated by IRS-1 through two independent, but convergent, pathways involving PI 3-kinase and GRB2. |
| 19 | 7961682 | Thus, microinjection of GST-fusion proteins of either p85 or GRB2 inhibited IRS-1-dependent activation of mitogen-activated protein (MAP) and S6 kinases and oocyte maturation, although only the GST-SH2 of p85 reduced insulin-stimulated PI 3-kinase activation. |
| 20 | 7961682 | Co-injection of a dominant negative Ras (S17N) with IRS-1 inhibited insulin-stimulated MAP and S6 kinase activation. |
| 21 | 7961682 | Micro-injection of activated [Arg12,Thr59]Ras increased basal MAP and S6 kinase activities and sensitized the oocytes to insulin-stimulated maturation without altering insulin-stimulated PI 3-kinase. |
| 22 | 7961682 | These data strongly suggest that IRS-1 can mediate many of insulin's actions on cellular enzyme activation and cell cycle progression requires binding and activation of multiple different SH2-domain proteins. |
| 23 | 7961682 | Interactive roles of Ras, insulin receptor substrate-1, and proteins with Src homology-2 domains in insulin signaling in Xenopus oocytes. |
| 24 | 7961682 | Insulin receptor substrate-1 (IRS-1) serves as the major immediate substrate of insulin/insulin-like growth factor (IGF)-1 receptors and following tyrosine phosphorylation binds to specific Src homology-2 (SH2) domain-containing proteins including the p85 subunit of phosphatidylinositol (PI) 3-kinase and GRB2, a molecule believed to link IRS-1 to the Ras pathway. |
| 25 | 7961682 | To investigate how these SH2-containing signaling molecules interact to regulate insulin/IGF-1 action, IRS-1, glutathione S-transferase (GST)-SH2 domain fusion proteins and Ras proteins were microinjected into Xenopus oocytes. |
| 26 | 7961682 | We found that pleiotropic insulin actions are mediated by IRS-1 through two independent, but convergent, pathways involving PI 3-kinase and GRB2. |
| 27 | 7961682 | Thus, microinjection of GST-fusion proteins of either p85 or GRB2 inhibited IRS-1-dependent activation of mitogen-activated protein (MAP) and S6 kinases and oocyte maturation, although only the GST-SH2 of p85 reduced insulin-stimulated PI 3-kinase activation. |
| 28 | 7961682 | Co-injection of a dominant negative Ras (S17N) with IRS-1 inhibited insulin-stimulated MAP and S6 kinase activation. |
| 29 | 7961682 | Micro-injection of activated [Arg12,Thr59]Ras increased basal MAP and S6 kinase activities and sensitized the oocytes to insulin-stimulated maturation without altering insulin-stimulated PI 3-kinase. |
| 30 | 7961682 | These data strongly suggest that IRS-1 can mediate many of insulin's actions on cellular enzyme activation and cell cycle progression requires binding and activation of multiple different SH2-domain proteins. |
| 31 | 8048169 | Insulin-receptor substrate 1 (IRS-1) is a principal substrate of the receptor tyrosine kinase for insulin and insulin-like growth factor 1, and a substrate for a tyrosine kinase activated by interleukin 4. |
| 32 | 8048169 | IRS-1 undergoes multisite tyrosine phosphorylation and mediates downstream signals by 'docking' various proteins that contain Src homology 2 domains. |
| 33 | 8382612 | An example of such phosphoprotein-effector coupling is provided by the association of phosphatidylinositol 3-kinase (PI 3-kinase) with specific phosphorylation sites within the PDGF receptor, the c-Src/polyoma virus middle T antigen complex and the insulin receptor substrate IRS-1. |
| 34 | 8382612 | To investigate how phosphoprotein binding to the p85 SH2 domain stimulates p110 catalytic activation, we have examined the differential effects of phosphotyrosine and PDGF receptor-, IRS-1- and c-Src-derived phosphopeptides on the conformation of an isolated SH2 domain of PI 3-kinase. |
| 35 | 8382612 | An example of such phosphoprotein-effector coupling is provided by the association of phosphatidylinositol 3-kinase (PI 3-kinase) with specific phosphorylation sites within the PDGF receptor, the c-Src/polyoma virus middle T antigen complex and the insulin receptor substrate IRS-1. |
| 36 | 8382612 | To investigate how phosphoprotein binding to the p85 SH2 domain stimulates p110 catalytic activation, we have examined the differential effects of phosphotyrosine and PDGF receptor-, IRS-1- and c-Src-derived phosphopeptides on the conformation of an isolated SH2 domain of PI 3-kinase. |
| 37 | 8631859 | The Fyn tyrosine kinase binds Irs-1 and forms a distinct signaling complex during insulin stimulation. |
| 38 | 8631859 | Irs-proteins link the receptors for insulin/IGF-1, growth hormones, and several interleukins and interferons to signaling proteins that contain Src homology-2 (SH2). |
| 39 | 8631859 | Mutation of p59fyn at the COOH-terminal tyrosine phosphorylation site (Tyr531) enhanced its binding to Irs-1 during insulin stimulation. |
| 40 | 8631859 | Binding experiments with various SH2 protein revealed that Grb-2 was largely excluded from Irs-1 complexes containing p59fyn, whereas Grb-2 and p85 occurred in the same Irs-1 complex. |
| 41 | 8631859 | By comparison with the insulin receptor, p59fyn kinase phosphorylated a unique cohort of tyrosine residues in Irs-1. |
| 42 | 8636261 | RNA from the proto-oncogenes c-Ha-ras, c-myc, and c-src transiently increased 2- to 4-fold within 30 min of insulin infusion. |
| 43 | 8636261 | In addition, the RNA abundance of myf-5, a muscle specific differentiation factor, increased 3-fold with a time course similar to that of c-Ha-ras, c-myc, and c-src. |
| 44 | 8636261 | In insulin-resistant individuals, the RNA levels of c-Ha-ras and myf-5 did not increase, whereas c-src RNA did increase within 30 min of insulin infusion. |
| 45 | 8636261 | RNA encoding c-myc transiently increased in both groups; however, this response was lower in insulin-resistant individuals than in insulin-sensitive individuals in a pattern similar to c-Ha-ras and myf-5. |
| 46 | 8636261 | PPP1A RNA levels slightly increased in insulin-resistant individuals. |
| 47 | 8636261 | In both insulin-sensitive and insulin-resistant persons, RNA quantities of GLUT4, c-jun, c-fos, and the insulin receptor did not change over the period of insulin infusion. |
| 48 | 8636261 | However, overall RNA levels of the insulin receptor and c-jun were lower in insulin-resistant individuals. |
| 49 | 8636261 | RNA from the proto-oncogenes c-Ha-ras, c-myc, and c-src transiently increased 2- to 4-fold within 30 min of insulin infusion. |
| 50 | 8636261 | In addition, the RNA abundance of myf-5, a muscle specific differentiation factor, increased 3-fold with a time course similar to that of c-Ha-ras, c-myc, and c-src. |
| 51 | 8636261 | In insulin-resistant individuals, the RNA levels of c-Ha-ras and myf-5 did not increase, whereas c-src RNA did increase within 30 min of insulin infusion. |
| 52 | 8636261 | RNA encoding c-myc transiently increased in both groups; however, this response was lower in insulin-resistant individuals than in insulin-sensitive individuals in a pattern similar to c-Ha-ras and myf-5. |
| 53 | 8636261 | PPP1A RNA levels slightly increased in insulin-resistant individuals. |
| 54 | 8636261 | In both insulin-sensitive and insulin-resistant persons, RNA quantities of GLUT4, c-jun, c-fos, and the insulin receptor did not change over the period of insulin infusion. |
| 55 | 8636261 | However, overall RNA levels of the insulin receptor and c-jun were lower in insulin-resistant individuals. |
| 56 | 8636261 | RNA from the proto-oncogenes c-Ha-ras, c-myc, and c-src transiently increased 2- to 4-fold within 30 min of insulin infusion. |
| 57 | 8636261 | In addition, the RNA abundance of myf-5, a muscle specific differentiation factor, increased 3-fold with a time course similar to that of c-Ha-ras, c-myc, and c-src. |
| 58 | 8636261 | In insulin-resistant individuals, the RNA levels of c-Ha-ras and myf-5 did not increase, whereas c-src RNA did increase within 30 min of insulin infusion. |
| 59 | 8636261 | RNA encoding c-myc transiently increased in both groups; however, this response was lower in insulin-resistant individuals than in insulin-sensitive individuals in a pattern similar to c-Ha-ras and myf-5. |
| 60 | 8636261 | PPP1A RNA levels slightly increased in insulin-resistant individuals. |
| 61 | 8636261 | In both insulin-sensitive and insulin-resistant persons, RNA quantities of GLUT4, c-jun, c-fos, and the insulin receptor did not change over the period of insulin infusion. |
| 62 | 8636261 | However, overall RNA levels of the insulin receptor and c-jun were lower in insulin-resistant individuals. |
| 63 | 8754813 | Tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) by the activated receptors for insulin, IGF-1, and various cytokines creates binding sites for signaling proteins with Src homology 2 domains (SH2 proteins). |
| 64 | 8754813 | Determining the role of specific SH2 proteins during insulin signaling has been difficult because IRS-1 possesses as many as 18 potential tyrosine phosphorylation sites, several of which contain redundant motifs. |
| 65 | 8754813 | Using 32D cells, which contain no endogenous IRS proteins, we compared the signaling ability of an IRS-1 molecule in which 18 potential tyrosine phosphorylation sites were replaced by phenylalanine (IRS-1(F18)) with two derivative molecules which retained three YMXM motifs (IRS-1(3YMXM)) or the two COOH-terminal SHP2-Fyn binding sites (IRS-1(YCT)). |
| 66 | 8754813 | During insulin stimulation, IRS-1(F18) failed to undergo tyrosine phosphorylation or mediate activation of the phosphotidylinositol (PI) 3'-kinase or p70(s6k); IRS-1(YCT) was tyrosine phosphorylated but also failed to mediate these signaling events. |
| 67 | 8754813 | IRS-1(F18) and IRS-1(YCT) partially mediated similar levels of insulin-stimulated mitogenesis at high insulin concentrations, however, suggesting that IRS-1 contains phosphotyrosine-independent elements which effect mitogenic signals, and that the sites in IRS-l(YCT) do not augment this signal. |
| 68 | 8754813 | IRS-1(3YMXM) mediated the maximal mitogenic response to insulin, although the response to insulin was more sensitive with wild-type IRS-1. |
| 69 | 8754813 | By contrast, the association of IRS-1(3YMXM) with PI 3'-kinase was more sensitive to insulin than the association with IRS-1. |
| 70 | 9598824 | We also propose a model of signal transduction for the endothelial cell response to shear stress including possible mechanotransducers (integrins, caveolae, ion channels, and G proteins), intermediate signaling molecules (c-Src, ras, Raf, protein kinase C) and the mitogen activated protein kinases (ERK1/2, JNK, p38, BMK-1), and effector molecules (nitric oxide). |
| 71 | 10660596 | Tyrosine dephosphorylation and deactivation of insulin receptor substrate-1 by protein-tyrosine phosphatase 1B. |
| 72 | 10660596 | The specific activity of four candidate protein-tyrosine phosphatases (protein-tyrosine phosphatase 1B (PTP1B), SH2 domain-containing PTPase-2 (SHP-2), leukocyte common antigen-related (LAR), and leukocyte antigen-related phosphatase) (LRP) toward IRS-1 dephosphorylation was studied using recombinant proteins in vitro. |
| 73 | 10660596 | When evaluated as a ratio of activity versus IRS-1 to that versus p-nitrophenyl phosphate, PTP1B remained significantly more active by 3.1-293-fold, respectively. |
| 74 | 10660596 | Overlay blots with recombinant Src homology 2 domains of IRS-1 adaptor proteins showed that the loss of IRS-1 binding of Crk, GRB2, SHP-2, and the p85 subunit of phosphatidylinositol 3'-kinase paralleled the rate of overall IRS-1 dephosphorylation. |
| 75 | 10660596 | Further studies revealed that the adaptor protein GRB2 strongly promoted the formation of a stable protein complex between tyrosine-phosphorylated IRS-1 and catalytically inactive PTP1B, increasing their co-immunoprecipitation from an equimolar solution by 13.5 +/- 3.3-fold (n = 7; p < 0.01). |
| 76 | 10660596 | Inclusion of GRB2 in a reaction mixture of IRS-1 and active PTP1B also increased the overall rate of IRS-1 tyrosine dephosphorylation by 2.7-3.9-fold (p < 0.01). |
| 77 | 10660596 | These results provide new insight into novel molecular interactions involving PTP1B and GRB2 that may influence the steady-state capacity of IRS-1 to function as a phosphotyrosine scaffold and possibly affect the balance of postreceptor insulin signaling. |
| 78 | 10866039 | We studied the impact of 16 serine residues in HIR by mutation to alanine and co-overexpression in human embryonic kidney (HEK) 293 cells together with the docking proteins insulin receptor substrate (IRS)-1, IRS-2, or (SHC) Src homologous and collagen-like. |
| 79 | 10866039 | Coexpression of HIR with IRS-1, IRS-2, and SHC strongly enhanced tyrosine phosphorylation of these proteins. |
| 80 | 10866039 | A similar increase in tyrosine phosphorylation was observed in cells overexpressing IRS-1, IRS-2, or SHC together with all HIR mutants except HIR delta JM and a mutant carrying exchanges of serines 1177, 1178, and 1182 to alanine (HIR1177/78/82), although this mutant showed normal autophosphorylation. |
| 81 | 10905491 | Tumor necrosis factor-alpha induces hepatic insulin resistance in obese Zucker (fa/fa) rats via interaction of leukocyte antigen-related tyrosine phosphatase with focal adhesion kinase. |
| 82 | 10905491 | The molecular mechanism whereby tumor necrosis factor-alpha (TNF-alpha) induces insulin resistance in obesity is not well understood. |
| 83 | 10905491 | Previously, we have shown that inhibition of TNF-alpha improved hepatic insulin sensitivity in obese Zucker rats without altering the tyrosine phosphorylation of liver insulin receptors (IRs), which indicates that the TNF-alpha and insulin-signaling cascades interact distally to the IR. |
| 84 | 10905491 | To assess the effects of TNF-alpha on signaling molecules downstream from the IR, we analyzed the tyrosine phosphorylation patterns of liver homogenate proteins from TNF-alpha-neutralized fa/fa rats and showed that focal adhesion kinase (FAK) was consistently hyperphosphorylated (4.5-fold). |
| 85 | 10905491 | Moreover, intravenous insulin increased hepatic FAK phosphorylation in a time-dependent manner in Sprague-Dawley rats, which suggests that TNF-alpha may induce hepatic insulin resistance by preventing FAK phosphorylation in response to insulin treatment. |
| 86 | 10905491 | To explore the cellular mechanism whereby TNF-alpha regulates phosphorylation of FAK in the liver, we measured c-Src kinase activity and the abundance of 3 major protein tyrosine phosphatases (PTPs) (PTP-1B, leukocyte antigen-related tyrosine phosphatase [LAR], and src homology 2 domain-containing protein-tyrosine phosphatase [SHPTP-2]) in liver homogenates from obese Zucker rats after TNF-alpha blockade. |
| 87 | 10905491 | Hepatic c-Src kinase activity was unaltered, but LAR protein was reduced by 75%. |
| 88 | 10905491 | In addition, TNF-alpha blockade reduced hepatic PTP activity toward tyrosine phosphorylated FAK by 70%, and this was accounted for by immunodepletion of LAR. |
| 89 | 10905491 | Incubation of HepG2 cells with TNF-alpha increased LAR protein levels in a dose-dependent manner. |
| 90 | 10905491 | Additionally, pretreatment with TNF-alpha abolished insulin-stimulated tyrosine phosphorylation of FAK in HepG2 cells but had no effect on IR tyrosine phosphorylation or expression. |
| 91 | 10905491 | These data suggest that TNF-alpha promotes LAR expression and thus prevents insulin-mediated tyrosine phosphorylation of FAK. |
| 92 | 10905491 | This probably represents the interface between TNF-alpha and insulin signaling in the liver. |
| 93 | 10905491 | Tumor necrosis factor-alpha induces hepatic insulin resistance in obese Zucker (fa/fa) rats via interaction of leukocyte antigen-related tyrosine phosphatase with focal adhesion kinase. |
| 94 | 10905491 | The molecular mechanism whereby tumor necrosis factor-alpha (TNF-alpha) induces insulin resistance in obesity is not well understood. |
| 95 | 10905491 | Previously, we have shown that inhibition of TNF-alpha improved hepatic insulin sensitivity in obese Zucker rats without altering the tyrosine phosphorylation of liver insulin receptors (IRs), which indicates that the TNF-alpha and insulin-signaling cascades interact distally to the IR. |
| 96 | 10905491 | To assess the effects of TNF-alpha on signaling molecules downstream from the IR, we analyzed the tyrosine phosphorylation patterns of liver homogenate proteins from TNF-alpha-neutralized fa/fa rats and showed that focal adhesion kinase (FAK) was consistently hyperphosphorylated (4.5-fold). |
| 97 | 10905491 | Moreover, intravenous insulin increased hepatic FAK phosphorylation in a time-dependent manner in Sprague-Dawley rats, which suggests that TNF-alpha may induce hepatic insulin resistance by preventing FAK phosphorylation in response to insulin treatment. |
| 98 | 10905491 | To explore the cellular mechanism whereby TNF-alpha regulates phosphorylation of FAK in the liver, we measured c-Src kinase activity and the abundance of 3 major protein tyrosine phosphatases (PTPs) (PTP-1B, leukocyte antigen-related tyrosine phosphatase [LAR], and src homology 2 domain-containing protein-tyrosine phosphatase [SHPTP-2]) in liver homogenates from obese Zucker rats after TNF-alpha blockade. |
| 99 | 10905491 | Hepatic c-Src kinase activity was unaltered, but LAR protein was reduced by 75%. |
| 100 | 10905491 | In addition, TNF-alpha blockade reduced hepatic PTP activity toward tyrosine phosphorylated FAK by 70%, and this was accounted for by immunodepletion of LAR. |
| 101 | 10905491 | Incubation of HepG2 cells with TNF-alpha increased LAR protein levels in a dose-dependent manner. |
| 102 | 10905491 | Additionally, pretreatment with TNF-alpha abolished insulin-stimulated tyrosine phosphorylation of FAK in HepG2 cells but had no effect on IR tyrosine phosphorylation or expression. |
| 103 | 10905491 | These data suggest that TNF-alpha promotes LAR expression and thus prevents insulin-mediated tyrosine phosphorylation of FAK. |
| 104 | 10905491 | This probably represents the interface between TNF-alpha and insulin signaling in the liver. |
| 105 | 10973497 | DAF-16 recruits the CREB-binding protein coactivator complex to the insulin-like growth factor binding protein 1 promoter in HepG2 cells. |
| 106 | 10973497 | Insulin negatively regulates expression of the insulin-like growth factor binding protein 1 (IGFBP-1) gene by means of an insulin-responsive element (IRE) that also contributes to glucocorticoid stimulation of this gene. |
| 107 | 10973497 | We find that the Caenorhabditis elegans protein DAF-16 binds the IGFBP-1 small middle dotIRE with specificity similar to that of the forkhead (FKH) factor(s) that act both to enhance glucocorticoid responsiveness and to mediate the negative effect of insulin at this site. |
| 108 | 10973497 | In HepG2 cells, DAF-16 and its mammalian homologs, FKHR, FKHRL1, and AFX, activate transcription through the IGFBP-1.IRE; this effect is inhibited by the viral oncoprotein E1A, but not by mutants of E1A that fail to interact with the coactivator p300/CREB-binding protein (CBP). |
| 109 | 10973497 | We show that DAF-16 and FKHR can interact with both the KIX and E1A/SRC interaction domains of p300/CBP, as well as the steroid receptor coactivator (SRC). |
| 110 | 10973497 | A C-terminal deletion mutant of DAF-16 that is nonfunctional in C. elegans fails to bind the KIX domain of CBP, fails to activate transcription through the IGFBP-1.IRE, and inhibits activation of the IGFBP-1 promoter by glucocorticoids. |
| 111 | 10973497 | Although AFX interacts with the KIX domain of CBP, it does not interact with SRC and does not respond to glucocorticoids or insulin. |
| 112 | 10973497 | Thus, we conclude that DAF-16 and FKHR act as accessory factors to the glucocorticoid response, by recruiting the p300/CBP/SRC coactivator complex to an FKH factor site in the IGFBP-1 promoter, which allows the cell to integrate the effects of glucocorticoids and insulin on genes that carry this site. |
| 113 | 11160694 | Soluble mediators such as interleukin-1beta, tumor necrosis factor alpha (TNF-alpha), and inducible nitric oxide synthase (iNOS) produced from activated macrophages play an important role in the destruction of pancreatic beta cells in mice infected with a low dose of the D variant of encephalomyocarditis (EMC-D) virus. |
| 114 | 11160694 | We examined the activation of p59/p56(Hck), p55(Fgr), and p56/p53(Lyn) in macrophages from DBA/2 mice infected with the virus. |
| 115 | 11160694 | We found that p59/p56(Hck) showed a marked increase in both autophosphorylation and kinase activity at 48 h after infection, whereas p55(Fgr) and p56/p53(Lyn) did not. |
| 116 | 11160694 | The p59/p56(Hck) activity was closely correlated with the tyrosine phosphorylation level of Vav. |
| 117 | 11160694 | Treatment of EMC-D virus-infected mice with the Src kinase inhibitor, PP2, resulted in the inhibition of p59/p56(Hck) activity and almost complete inhibition of the production of TNF-alpha and iNOS in macrophages and the subsequent prevention of diabetes in mice. |
| 118 | 11160694 | On the basis of these observations, we conclude that the Src kinase, p59/p56(Hck), plays an important role in the activation of macrophages and the subsequent production of TNF-alpha and nitric oxide, leading to the destruction of pancreatic beta cells, which results in the development of diabetes in mice infected with a low dose of EMC-D virus. |
| 119 | 11160694 | Soluble mediators such as interleukin-1beta, tumor necrosis factor alpha (TNF-alpha), and inducible nitric oxide synthase (iNOS) produced from activated macrophages play an important role in the destruction of pancreatic beta cells in mice infected with a low dose of the D variant of encephalomyocarditis (EMC-D) virus. |
| 120 | 11160694 | We examined the activation of p59/p56(Hck), p55(Fgr), and p56/p53(Lyn) in macrophages from DBA/2 mice infected with the virus. |
| 121 | 11160694 | We found that p59/p56(Hck) showed a marked increase in both autophosphorylation and kinase activity at 48 h after infection, whereas p55(Fgr) and p56/p53(Lyn) did not. |
| 122 | 11160694 | The p59/p56(Hck) activity was closely correlated with the tyrosine phosphorylation level of Vav. |
| 123 | 11160694 | Treatment of EMC-D virus-infected mice with the Src kinase inhibitor, PP2, resulted in the inhibition of p59/p56(Hck) activity and almost complete inhibition of the production of TNF-alpha and iNOS in macrophages and the subsequent prevention of diabetes in mice. |
| 124 | 11160694 | On the basis of these observations, we conclude that the Src kinase, p59/p56(Hck), plays an important role in the activation of macrophages and the subsequent production of TNF-alpha and nitric oxide, leading to the destruction of pancreatic beta cells, which results in the development of diabetes in mice infected with a low dose of EMC-D virus. |
| 125 | 11230339 | Angiotensin II induces migration and Pyk2/paxillin phosphorylation of human monocytes. |
| 126 | 11230339 | Addition of the Ang II receptor type 1 (AT1-R) antagonist losartan (1 to 100 micromol/L) suppressed Ang II-induced migration of HPBM and THP-1 monocytes in a dose-dependent manner, demonstrating an AT1-R-mediated mechanism. |
| 127 | 11230339 | Ang II-directed migration was also blocked by the Src kinase inhibitor PP2 (10 micromol/L), by the extracellular-regulated protein kinase (ERK 1/2) inhibitor PD98059 (30 micromol/L), and by the p38-MAPK inhibitor SB203580 (10 micromol/L), indicating that Src, ERK 1/2, and p38 are all involved in Ang II-induced migration of HPBM and human THP-1 monocytes. |
| 128 | 11230339 | The proline-rich tyrosine kinase 2 (Pyk2) and paxillin are 2 cytoskeleton-associated proteins involved in cell movement, phosphorylated by Ang II in other cell types, and abundantly expressed in monocytes. |
| 129 | 11230339 | Ang II (1 micromol/L) induced Pyk2 and paxillin phosphorylation in human THP-1 monocytes, peaking after 10 minutes for Pyk2 with a 6.7+/-0.9-fold induction and after 2 minutes for paxillin with a 3.2+/-0.4-fold induction. |
| 130 | 11230339 | This study demonstrates a novel proatherogenic action of Ang II on human monocytes by stimulating their migration, through an AT1-R-dependent process, involving signaling through Src, ERK 1/2, and p38. |
| 131 | 11230339 | Furthermore, the promigratory actions of Ang II in human monocytes are associated with the phosphorylation of 2 cytoskeleton-associated proteins, Pyk2 and paxillin. |
| 132 | 11230339 | Angiotensin II induces migration and Pyk2/paxillin phosphorylation of human monocytes. |
| 133 | 11230339 | Addition of the Ang II receptor type 1 (AT1-R) antagonist losartan (1 to 100 micromol/L) suppressed Ang II-induced migration of HPBM and THP-1 monocytes in a dose-dependent manner, demonstrating an AT1-R-mediated mechanism. |
| 134 | 11230339 | Ang II-directed migration was also blocked by the Src kinase inhibitor PP2 (10 micromol/L), by the extracellular-regulated protein kinase (ERK 1/2) inhibitor PD98059 (30 micromol/L), and by the p38-MAPK inhibitor SB203580 (10 micromol/L), indicating that Src, ERK 1/2, and p38 are all involved in Ang II-induced migration of HPBM and human THP-1 monocytes. |
| 135 | 11230339 | The proline-rich tyrosine kinase 2 (Pyk2) and paxillin are 2 cytoskeleton-associated proteins involved in cell movement, phosphorylated by Ang II in other cell types, and abundantly expressed in monocytes. |
| 136 | 11230339 | Ang II (1 micromol/L) induced Pyk2 and paxillin phosphorylation in human THP-1 monocytes, peaking after 10 minutes for Pyk2 with a 6.7+/-0.9-fold induction and after 2 minutes for paxillin with a 3.2+/-0.4-fold induction. |
| 137 | 11230339 | This study demonstrates a novel proatherogenic action of Ang II on human monocytes by stimulating their migration, through an AT1-R-dependent process, involving signaling through Src, ERK 1/2, and p38. |
| 138 | 11230339 | Furthermore, the promigratory actions of Ang II in human monocytes are associated with the phosphorylation of 2 cytoskeleton-associated proteins, Pyk2 and paxillin. |
| 139 | 11278940 | c-Src tyrosine kinase binds the beta 2-adrenergic receptor via phospho-Tyr-350, phosphorylates G-protein-linked receptor kinase 2, and mediates agonist-induced receptor desensitization. |
| 140 | 11278940 | Downstream of binding to the receptor, Src phosphorylates and activates G-protein-linked receptor kinase 2 (GRK2), a response obligate for agonist-induced desensitization. |
| 141 | 11278940 | c-Src tyrosine kinase binds the beta 2-adrenergic receptor via phospho-Tyr-350, phosphorylates G-protein-linked receptor kinase 2, and mediates agonist-induced receptor desensitization. |
| 142 | 11278940 | Downstream of binding to the receptor, Src phosphorylates and activates G-protein-linked receptor kinase 2 (GRK2), a response obligate for agonist-induced desensitization. |
| 143 | 11598137 | Peroxisome proliferator-activated receptor gamma ligands inhibit mitogenic induction of p21(Cip1) by modulating the protein kinase Cdelta pathway in vascular smooth muscle cells. |
| 144 | 11598137 | PPARgamma ligands troglitazone (TRO, 10 microm) and rosiglitazone (RSG, 10 microm) attenuated the induction of p21(Cip1) protein by platelet-derived growth factor (PDGF) and insulin without affecting cognate mRNA levels in rat aortic smooth muscle cells (RASMC). |
| 145 | 11598137 | Kinetic studies using the protein synthesis inhibitor cycloheximide showed that TRO, RSG, and rottlerin shortened the half-life of p21(Cip1) protein. |
| 146 | 11598137 | TRO, RSG, and rottlerin inhibited PDGF-induced expression of p21(Cip1), but they did not affect insulin-induced expression of p21(Cip1). |
| 147 | 11598137 | Both ligands inhibited PKCdelta enzymatic activity in PDGF-stimulated RASMC but not in insulin-stimulated cells. |
| 148 | 11598137 | Adenovirus-mediated overexpression of PKCdelta rescued the down-regulation of p21(Cip1) expression both by TRO and RSG in PDGF-treated RASMC. |
| 149 | 11598137 | These data suggested that the PKCdelta pathway plays a critical role in PDGF-induced expression of p21(Cip1) in RASMC and may be the potential target for PPARgamma ligand effects. |
| 150 | 11598137 | Tyrosine phosphorylation and activation of c-Src in response to PDGF were unaffected by either PPARgamma ligand. |
| 151 | 11598137 | Both inhibitors also reversed PPARgamma ligand effects on p21(Cip1) expression in PDGF-treated RASMC. |
| 152 | 11598137 | PPARgamma ligands regulate p21(Cip1) at a post-translational level by blocking PKCdelta signaling and accelerating p21(Cip1) turnover. |
| 153 | 11788655 | Down-regulation of insulin receptor substrates (IRS)-1 and IRS-2 and Src homologous and collagen-like protein Shc gene expression by insulin in skeletal muscle is not associated with insulin resistance or type 2 diabetes. |
| 154 | 11788655 | To examine whether altered gene expression of insulin receptor substrates (IRS)-1 and IRS-2 and Src homologous and collagen-like protein Shc is an inherited trait and is associated with muscle insulin resistance or type 2 diabetes, we measured mRNA levels of these genes by a relative quantitative RT-PCR method in muscle biopsies taken before and after an insulin clamp from 12 monozygotic twin pairs discordant for type 2 diabetes and 12 control subjects. |
| 155 | 11788655 | Basal mRNA levels of IRS-1, IRS-2, and Shc were similar in the diabetic and nondiabetic twins as well as in the control subjects. |
| 156 | 11788655 | Insulin decreased mRNA expression of IRS-1 by 72% (from 0.75 +/- 0.06 to 0.21 +/- 0.04 relative units; P < 0.001), IRS-2 by 71% (from 0.55 +/- 0.10 to 0.16 +/- 0.08 relative units; P < 0.03), and Shc by 25% (from 0.95 +/- 0.04 to 0.71 +/- 0.04 relative units; P < 0.01) vs. baseline as demonstrated in the control subjects. |
| 157 | 11788655 | The postclamp Shc mRNA level was slightly higher in the diabetic twins (P = 0.05) but similar in the nondiabetic twins, as compared with the control subjects, whereas postclamp IRS-1 and IRS-2 mRNA levels were similar between the study groups. |
| 158 | 11788655 | However, the decrease in Shc gene expression by insulin was not significantly different between the study groups. |
| 159 | 11788655 | In conclusion, because insulin down-regulates IRS-1, IRS-2, and Shc gene expression in skeletal muscle in diabetic and nondiabetic monozygotic twins and control subjects to the same extent, it is unlikely that expression of these genes is an inherited trait or contributes to skeletal muscle insulin resistance. |
| 160 | 11788655 | Down-regulation of insulin receptor substrates (IRS)-1 and IRS-2 and Src homologous and collagen-like protein Shc gene expression by insulin in skeletal muscle is not associated with insulin resistance or type 2 diabetes. |
| 161 | 11788655 | To examine whether altered gene expression of insulin receptor substrates (IRS)-1 and IRS-2 and Src homologous and collagen-like protein Shc is an inherited trait and is associated with muscle insulin resistance or type 2 diabetes, we measured mRNA levels of these genes by a relative quantitative RT-PCR method in muscle biopsies taken before and after an insulin clamp from 12 monozygotic twin pairs discordant for type 2 diabetes and 12 control subjects. |
| 162 | 11788655 | Basal mRNA levels of IRS-1, IRS-2, and Shc were similar in the diabetic and nondiabetic twins as well as in the control subjects. |
| 163 | 11788655 | Insulin decreased mRNA expression of IRS-1 by 72% (from 0.75 +/- 0.06 to 0.21 +/- 0.04 relative units; P < 0.001), IRS-2 by 71% (from 0.55 +/- 0.10 to 0.16 +/- 0.08 relative units; P < 0.03), and Shc by 25% (from 0.95 +/- 0.04 to 0.71 +/- 0.04 relative units; P < 0.01) vs. baseline as demonstrated in the control subjects. |
| 164 | 11788655 | The postclamp Shc mRNA level was slightly higher in the diabetic twins (P = 0.05) but similar in the nondiabetic twins, as compared with the control subjects, whereas postclamp IRS-1 and IRS-2 mRNA levels were similar between the study groups. |
| 165 | 11788655 | However, the decrease in Shc gene expression by insulin was not significantly different between the study groups. |
| 166 | 11788655 | In conclusion, because insulin down-regulates IRS-1, IRS-2, and Shc gene expression in skeletal muscle in diabetic and nondiabetic monozygotic twins and control subjects to the same extent, it is unlikely that expression of these genes is an inherited trait or contributes to skeletal muscle insulin resistance. |
| 167 | 11897556 | Phosphoinositide 3-kinase (PI3K) plays a key role in insulin signaling and has been shown to be blunted in tissues of type 2 diabetes subjects. |
| 168 | 11897556 | There is emerging biochemical and, particularly, genetic evidence suggesting that insulin resistance can potentially be treated via modulation of PI3K by targeting PI3K itself or its up and down-stream modulators. |
| 169 | 11897556 | These potential targets include Src homology 2 domain containing inositol 5-phosphatase 2 (SHIP2), phosphatase and tensin homolog deleted on chromosome ten (PTEN), kappaB kinase beta (IKKbeta), PKC isoforms, and the PI3K p85 subunit. |
| 170 | 11897556 | There is evidence suggesting that their inhibition affects PI3K activity and improves insulin sensitivity in vivo. |
| 171 | 11897556 | In the current review, we will discuss the role of these molecules in insulin-mediated activation of PI3K, the rational for targeting these molecules for diabetes treatment, and some critical issues in terms of drug development. |
| 172 | 12351660 | The differentiation of skeletal muscle cells involves a protein-tyrosine phosphatase-alpha-mediated C-Src signaling pathway. |
| 173 | 12351660 | The different myogenic activities of these cell lines were correlated with the expression of myogenin and creatine kinase activity. |
| 174 | 12351660 | Consistent with previous reports, PTPalpha positively regulated the activity of the protein-tyrosine kinase Src. |
| 175 | 12351660 | Moreover, enhanced expression of PTPalpha and activation of Src was detected during myogenesis. |
| 176 | 12351660 | The differentiation of skeletal muscle cells involves a protein-tyrosine phosphatase-alpha-mediated C-Src signaling pathway. |
| 177 | 12351660 | The different myogenic activities of these cell lines were correlated with the expression of myogenin and creatine kinase activity. |
| 178 | 12351660 | Consistent with previous reports, PTPalpha positively regulated the activity of the protein-tyrosine kinase Src. |
| 179 | 12351660 | Moreover, enhanced expression of PTPalpha and activation of Src was detected during myogenesis. |
| 180 | 12351660 | The differentiation of skeletal muscle cells involves a protein-tyrosine phosphatase-alpha-mediated C-Src signaling pathway. |
| 181 | 12351660 | The different myogenic activities of these cell lines were correlated with the expression of myogenin and creatine kinase activity. |
| 182 | 12351660 | Consistent with previous reports, PTPalpha positively regulated the activity of the protein-tyrosine kinase Src. |
| 183 | 12351660 | Moreover, enhanced expression of PTPalpha and activation of Src was detected during myogenesis. |
| 184 | 12502502 | Glucagon-like peptide 1 induces pancreatic beta-cell proliferation via transactivation of the epidermal growth factor receptor. |
| 185 | 12502502 | We previously provided evidence that glucagon-like peptide 1 (GLP-1) induces pancreatic beta-cell growth nonadditively with glucose in a phosphatidylinositol (PI) 3-kinase- and protein kinase C zeta-dependent manner. |
| 186 | 12502502 | However, the exact mechanism by which the GLP-1 receptor (GLP-1R), a member of the G protein-coupled receptor (GPCR) superfamily, activates the PI 3-kinase signaling pathway to promote beta-cell growth remains unknown. |
| 187 | 12502502 | We hypothesized that the GLP-1R could activate PI 3-kinase and promote beta-cell proliferation through transactivation of the epidermal growth factor (EGF) receptor (EGFR), an event possibly linked to GPCRs via activation of c-Src and the production of putative endogenous EGF-like ligands. |
| 188 | 12502502 | Both the c-Src inhibitor PP1 and the EGFR-specific inhibitor AG1478 blocked GLP-1-induced [(3)H]thymidine incorporation in INS(832/13) cells as well as in isolated rat islets, while only AG1478 inhibited the proliferative action of betacellulin (BTC), an EGFR agonist. |
| 189 | 12502502 | A time-dependent increase in tyrosine phosphorylation of the EGFR in response to GLP-1 was observed in INS(832/13) cells. |
| 190 | 12502502 | This transactivation of the EGFR was sensitive to both the pharmacological agents PP1 and AG1478. |
| 191 | 12502502 | The action of GLP-1 and BTC on INS cell proliferation was found to be not additive. |
| 192 | 12502502 | GLP-1 treatment of INS cells caused a decrease in cell surface-associated BTC, as shown by FACS analysis. |
| 193 | 12502502 | The results are consistent with a model in which GLP-1 increases PI 3-kinase activity and enhances beta-cell proliferation via transactivation of the EGFR that would require the proteolytic processing of membrane-anchored BTC or other EGF-like ligands. |
| 194 | 12502502 | Glucagon-like peptide 1 induces pancreatic beta-cell proliferation via transactivation of the epidermal growth factor receptor. |
| 195 | 12502502 | We previously provided evidence that glucagon-like peptide 1 (GLP-1) induces pancreatic beta-cell growth nonadditively with glucose in a phosphatidylinositol (PI) 3-kinase- and protein kinase C zeta-dependent manner. |
| 196 | 12502502 | However, the exact mechanism by which the GLP-1 receptor (GLP-1R), a member of the G protein-coupled receptor (GPCR) superfamily, activates the PI 3-kinase signaling pathway to promote beta-cell growth remains unknown. |
| 197 | 12502502 | We hypothesized that the GLP-1R could activate PI 3-kinase and promote beta-cell proliferation through transactivation of the epidermal growth factor (EGF) receptor (EGFR), an event possibly linked to GPCRs via activation of c-Src and the production of putative endogenous EGF-like ligands. |
| 198 | 12502502 | Both the c-Src inhibitor PP1 and the EGFR-specific inhibitor AG1478 blocked GLP-1-induced [(3)H]thymidine incorporation in INS(832/13) cells as well as in isolated rat islets, while only AG1478 inhibited the proliferative action of betacellulin (BTC), an EGFR agonist. |
| 199 | 12502502 | A time-dependent increase in tyrosine phosphorylation of the EGFR in response to GLP-1 was observed in INS(832/13) cells. |
| 200 | 12502502 | This transactivation of the EGFR was sensitive to both the pharmacological agents PP1 and AG1478. |
| 201 | 12502502 | The action of GLP-1 and BTC on INS cell proliferation was found to be not additive. |
| 202 | 12502502 | GLP-1 treatment of INS cells caused a decrease in cell surface-associated BTC, as shown by FACS analysis. |
| 203 | 12502502 | The results are consistent with a model in which GLP-1 increases PI 3-kinase activity and enhances beta-cell proliferation via transactivation of the EGFR that would require the proteolytic processing of membrane-anchored BTC or other EGF-like ligands. |
| 204 | 12730241 | Because the other known PH-PTB proteins (insulin receptor substrates: IRS-1, IRS-2, IRS-3, and IRS-4, and the downstream of kinases: DOK-1, DOK-2, and DOK-3) are substrates of insulin and insulin-like growth factor (IGF)-1 receptors, we asked whether these new proteins, termed IRS5/DOK4 and IRS6/DOK5, might also have roles in insulin and IGF-1 signaling. |
| 205 | 12730241 | Both proteins are tyrosine-phosphorylated in response to insulin and IGF-1 in transfected cells, although the kinetics differ. |
| 206 | 12730241 | Insulin receptor-phosphorylated IRS5/DOK4 associates with RasGAP, Crk, Src, and Fyn, but not phosphatidylinositol 3-kinase p85, Grb2, SHP-2, Nck, or phospholipase Cgamma Src homology 2 domains, and activates MAPK in cells. |
| 207 | 12730241 | IRS5/DOK4 and IRS6/DOK5 represent two new signaling proteins with potential roles in insulin and IGF-1 action. |
| 208 | 14568990 | Role of the pleckstrin homology domain of PLCgamma1 in its interaction with the insulin receptor. |
| 209 | 14568990 | A thiol-reactive membrane-associated protein (TRAP) binds covalently to the cytoplasmic domain of the human insulin receptor (IR) beta-subunit when cells are treated with the homobifunctional cross-linker reagent 1,6-bismaleimidohexane. |
| 210 | 14568990 | Here, TRAP was found to be phospholipase C gamma1 (PLCgamma1) by mass spectrometry analysis. |
| 211 | 14568990 | Insulin increased PLCgamma1 tyrosine phosphorylation at Tyr-783 and its colocalization with the IR in punctated structures enriched in cortical actin at the dorsal plasma membrane. |
| 212 | 14568990 | This association was found to be independent of PLCgamma1 Src homology 2 domains, and instead required the pleckstrin homology (PH)-EF-hand domain. |
| 213 | 14568990 | Expression of the PH-EF construct blocked endogenous PLCgamma1 binding to the IR and inhibited insulin-dependent phosphorylation of mitogen-activated protein kinase (MAPK), but not AKT. |
| 214 | 14568990 | Silencing PLCgamma1 expression using small interfering RNA markedly reduced insulin-dependent MAPK regulation in HepG2 cells. |
| 215 | 14568990 | Conversely, reconstitution of PLCgamma1 in PLCgamma1-/- fibroblasts improved MAPK activation by insulin. |
| 216 | 14568990 | Our results show that PLCgamma1 is a thiol-reactive protein whose association with the IR could contribute to the activation of MAPK signaling by insulin. |
| 217 | 15044356 | GLP-1 receptor activation enhances beta-cell proliferation and promotes islet neogenesis via activation of pdx-1 expression. |
| 218 | 15044356 | The proliferative effects of GLP-1 appear to involve multiple intracellular pathways, including stimulation of Akt, activation of protein kinase Czeta, and transactivation of the epidermal growth factor receptor through the c-src kinase. |
| 219 | 15044356 | GLP-1 receptor activation also promotes cell survival in beta-cells and neurons via increased levels of cAMP leading to cAMP response element binding protein activation, enhanced insulin receptor substrate-2 activity and, ultimately, activation of Akt. |
| 220 | 15265871 | Further, either depletion of mitochondria or adenoviral overexpression of superoxide dismutases, as well as inhibition of nitric-oxide synthase, abolished the metformin-enhanced phosphorylations and activities of AMPK, implicating that activation of AMPK by metformin might be mediated by the mitochondria-derived RNS. |
| 221 | 15265871 | Furthermore, administration of metformin, which increased 3-nitrotyrosine staining in hearts of C57BL6, resulted in parallel activation of AMPK in the aorta and hearts of C57BL6 mice but not in those of endothelial nitric-oxide synthase (eNOS) knockout mice in which metformin had no effect on 3-nitrotyrosine staining. |
| 222 | 15265871 | Because the eNOS knockout mice expressed normal levels of AMPK-alpha that was activated by 5-aminoimidazole-4-carboxamide riboside, an AMPK agonist, these data indicate that RNS generated by metformin is required for AMPK activation in vivo. |
| 223 | 15265871 | In addition, metformin significantly increased the co-immunoprecipitation of AMPK and its upstream kinase, LKB1, in C57BL6 mice administered to metformin in vivo. |
| 224 | 15265871 | Using pharmacological and genetic inhibitors, we found that inhibition of either c-Src or PI3K abolished AMPK that was enhanced by metformin. |
| 225 | 15265871 | We conclude that activation of AMPK by metformin might be mediated by mitochondria-derived RNS, and activation of the c-Src/PI3K pathway might generate a metabolite or other molecule inside the cell to promote AMPK activation by the LKB1 complex. |
| 226 | 15265871 | Further, either depletion of mitochondria or adenoviral overexpression of superoxide dismutases, as well as inhibition of nitric-oxide synthase, abolished the metformin-enhanced phosphorylations and activities of AMPK, implicating that activation of AMPK by metformin might be mediated by the mitochondria-derived RNS. |
| 227 | 15265871 | Furthermore, administration of metformin, which increased 3-nitrotyrosine staining in hearts of C57BL6, resulted in parallel activation of AMPK in the aorta and hearts of C57BL6 mice but not in those of endothelial nitric-oxide synthase (eNOS) knockout mice in which metformin had no effect on 3-nitrotyrosine staining. |
| 228 | 15265871 | Because the eNOS knockout mice expressed normal levels of AMPK-alpha that was activated by 5-aminoimidazole-4-carboxamide riboside, an AMPK agonist, these data indicate that RNS generated by metformin is required for AMPK activation in vivo. |
| 229 | 15265871 | In addition, metformin significantly increased the co-immunoprecipitation of AMPK and its upstream kinase, LKB1, in C57BL6 mice administered to metformin in vivo. |
| 230 | 15265871 | Using pharmacological and genetic inhibitors, we found that inhibition of either c-Src or PI3K abolished AMPK that was enhanced by metformin. |
| 231 | 15265871 | We conclude that activation of AMPK by metformin might be mediated by mitochondria-derived RNS, and activation of the c-Src/PI3K pathway might generate a metabolite or other molecule inside the cell to promote AMPK activation by the LKB1 complex. |
| 232 | 15314154 | Disruption of the SH2-B gene causes age-dependent insulin resistance and glucose intolerance. |
| 233 | 15314154 | SH2-B, an Src homology 2 (SH2) and pleckstrin homology domain-containing adaptor protein, binds via its SH2 domain to insulin receptor in response to insulin; however, its physiological role remains unclear. |
| 234 | 15314154 | Systemic deletion of SH2-B impaired insulin receptor activation and signaling in the liver, skeletal muscle, and fat, including tyrosine phosphorylation of insulin receptor substrate 1 (IRS1) and IRS2 and activation of the phosphatidylinositol 3-kinase/Akt and the Erk1/2 pathways. |
| 235 | 15314154 | Moreover, SH2-B directly enhanced autophosphorylation of insulin receptor and tyrosine phosphorylation of IRS1 and IRS2 in an SH2 domain-dependent manner in cultured cells. |
| 236 | 15314154 | Our data suggest that SH2-B is a physiological enhancer of insulin receptor activation and is required for maintaining normal insulin sensitivity and glucose homeostasis during aging. |
| 237 | 15544473 | In the field of PTPs, the research was mainly focused on new and selective PTP1B inhibitors, possibly useful in the treatment of Type 2 diabetes. |
| 238 | 15544473 | Other neutral compounds, mainly quinones, were found to inhibit CD45 and Cdc25. |
| 239 | 15544473 | Several papers have appeared in recent years on the discovery of new Grb2, Src, Syk, and Lck SH2 domains binding antagonists. |
| 240 | 15544473 | As regards Grb2, Src and Lck SH2 domains, rigidification of the starting high affinity binding peptides afforded derivatives with improved affinity; cellular activity was achieved by modification of the side chains of these inhibitors. |
| 241 | 15544473 | In the field of PTPs, the research was mainly focused on new and selective PTP1B inhibitors, possibly useful in the treatment of Type 2 diabetes. |
| 242 | 15544473 | Other neutral compounds, mainly quinones, were found to inhibit CD45 and Cdc25. |
| 243 | 15544473 | Several papers have appeared in recent years on the discovery of new Grb2, Src, Syk, and Lck SH2 domains binding antagonists. |
| 244 | 15544473 | As regards Grb2, Src and Lck SH2 domains, rigidification of the starting high affinity binding peptides afforded derivatives with improved affinity; cellular activity was achieved by modification of the side chains of these inhibitors. |
| 245 | 15573145 | However, the localization of NMT is reversed by treatment with a calpain inhibitor (ALLM N-Ac-Leu-Leu-methioninal). |
| 246 | 15573145 | During ischemia-reperfusion, the degradation of c-Src, which is a substrate of NMT, was observed. |
| 247 | 15573145 | Streptozotocin-induced diabetes (an animal model for insulin-dependent diabetes mellitus) resulted in a 2.0-fold increase in rat liver NMT activity as compared with control animals. |
| 248 | 15573145 | In obese (fa/fa) Zucker rats (an animal model for non-insulin-dependent diabetes mellitus), there was an approximately 4.7-fold lower liver particulate NMT activity as compared with control lean rat livers. |
| 249 | 15573145 | These results would indicate that rat liver particulate NMT activity appears to be inversely proportional to the level of plasma insulin, implicating insulin in the control of N-myristoylation. |
| 250 | 15750341 | The Src/PLC/PKC/MEK/ERK signaling pathway is involved in aortic smooth muscle cell proliferation induced by glycated LDL. |
| 251 | 15750341 | We examined the effects of native LDL and glycated LDL on the extracellular signal-regulated kinase (ERK) pathway. |
| 252 | 15750341 | ERK phosphorylation was not affected by exposure to the Ca2+ chelator BAPTA-AM but inhibition of protein kinase C (PKC) with GF109203X, inhibition of Src kinase with PP1 (5 microM) and inhibition of phospholipase C (PLC) with U73122/U73343 (5 microM) all reduced ERK phosphorylation in response to glycated LDL. |
| 253 | 15750341 | These findings indicate that ERK phosphorylation in response to glycated LDL involves the activation of PKC, PLC, and MEK, but is independent of intracellular Ca2+. |
| 254 | 15866871 | Protein-tyrosine phosphatase 1B (PTP1B) is a key negative regulator of insulin and leptin signaling and a novel therapeutic target for the treatment of type 2 diabetes, obesity, and other associated metabolic syndromes. |
| 255 | 15866871 | We show that down-regulation of PTP1B activity with small molecule inhibitors suppresses cell spreading and migration to fibronectin, increases Tyr(527) phosphorylation in Src, and decreases phosphorylation of FAK, p130(Cas), and ERK1/2. |
| 256 | 15866871 | We also show that PTP1B forms a complex with Src and p130(Cas), and that the proline-rich motif PPRPPK (residues 309-314) in PTP1B is essential for the complex formation. |
| 257 | 15866871 | We suggest that the specificity of PTP1B for Src pTyr(527) is mediated by protein-protein interactions involving the docking protein p130(Cas) with both Src and PTP1B in addition to the interactions between the PTP1B active site and the pTyr(527) motif. |
| 258 | 15866871 | Protein-tyrosine phosphatase 1B (PTP1B) is a key negative regulator of insulin and leptin signaling and a novel therapeutic target for the treatment of type 2 diabetes, obesity, and other associated metabolic syndromes. |
| 259 | 15866871 | We show that down-regulation of PTP1B activity with small molecule inhibitors suppresses cell spreading and migration to fibronectin, increases Tyr(527) phosphorylation in Src, and decreases phosphorylation of FAK, p130(Cas), and ERK1/2. |
| 260 | 15866871 | We also show that PTP1B forms a complex with Src and p130(Cas), and that the proline-rich motif PPRPPK (residues 309-314) in PTP1B is essential for the complex formation. |
| 261 | 15866871 | We suggest that the specificity of PTP1B for Src pTyr(527) is mediated by protein-protein interactions involving the docking protein p130(Cas) with both Src and PTP1B in addition to the interactions between the PTP1B active site and the pTyr(527) motif. |
| 262 | 16141358 | Pleiotropic AT1 receptor signaling pathways mediating physiological and pathogenic actions of angiotensin II. |
| 263 | 16141358 | Angiotensin II (Ang II) activates a wide spectrum of signaling responses via the AT1 receptor (AT1R) that mediate its physiological control of blood pressure, thirst, and sodium balance and its diverse pathological actions in cardiovascular, renal, and other cell types. |
| 264 | 16141358 | Ang II-induced AT1R activation via Gq/11 stimulates phospholipases A2, C, and D, and activates inositol trisphosphate/Ca2+ signaling, protein kinase C isoforms, and MAPKs, as well as several tyrosine kinases (Pyk2, Src, Tyk2, FAK), scaffold proteins (G protein-coupled receptor kinase-interacting protein 1, p130Cas, paxillin, vinculin), receptor tyrosine kinases, and the nuclear factor-kappaB pathway. |
| 265 | 16141358 | The AT1R also signals via Gi/o and G11/12 and stimulates G protein-independent signaling pathways, such as beta-arrestin-mediated MAPK activation and the Jak/STAT. |
| 266 | 16141358 | Many of the deleterious actions of AT1R activation are initiated by locally generated, rather than circulating, Ang II and are concomitant with the harmful effects of aldosterone in the cardiovascular system. |
| 267 | 16141358 | The recognition of Ang II's pathogenic actions is leading to novel clinical applications of angiotensin-converting enzyme inhibitors and AT1R antagonists, in addition to their established therapeutic actions in essential hypertension. |
| 268 | 16344371 | Peroxisome proliferator-activated receptor gamma regulates angiotensin II-stimulated phosphatidylinositol 3-kinase and mitogen-activated protein kinase in blood vessels in vivo. |
| 269 | 16344371 | Angiotensin (Ang) II is implicated in hypertension, vascular remodeling, and insulin resistance. |
| 270 | 16344371 | Peroxisome proliferator-activated receptor (PPAR) gamma activators increase insulin sensitivity and improve Ang II-induced vascular remodeling. |
| 271 | 16344371 | We evaluated the effects of the PPAR-gamma activator rosiglitazone on Ang II signaling in aorta and mesenteric arteries. |
| 272 | 16344371 | Akt activity was increased by Ang II and returned to basal levels under rosiglitazone in both vascular beds. |
| 273 | 16344371 | However, Ang II-induced extracellular signal-regulated kinase 1/2 activity increased in aorta but not in mesenteric vessels (P<0.001), where 4E-binding protein 1 activity was significantly increased by Ang II and inhibited by PPAR-gamma activation. |
| 274 | 16344371 | In response to Ang II, Src homology (SH) 2-containing inositol phosphatase 2 activity was increased (P<0.05) in both vascular beds. |
| 275 | 16344371 | In conclusion, PPAR-gamma activator rosiglitazone attenuated Ang II-induced blood pressure elevation and intracellular signaling on aorta and mesenteric vessels. |
| 276 | 16344371 | There was differential inhibition of Ang II type 1 receptor receptors/phosphatidylinositol 3-kinase/Akt and extracellular signal-regulated kinase 1/2 in both vessels. |
| 277 | 16767106 | Angiotensin II-dependent Src and Smad1 signaling pathway is crucial for the development of diabetic nephropathy. |
| 278 | 16767106 | We have reported that Smad1 plays a key role in diabetic mesangial matrix expansion and directly regulates the transcription of type IV collagen (Col4) in vitro and in vivo. |
| 279 | 16767106 | Here we examined the effect of Ang II on the expression of Smad1 and mesangial matrix expansion in streptozotocin (STZ)-induced diabetic rats in vivo, using Ang II type 1 receptor blocker, olmesartan. |
| 280 | 16767106 | Ang II induced Col4 synthesis and increased expression of phospho-Src and phospho-Smad1 in cultured mesangial cells, which was blocked by olmesartan. |
| 281 | 16767106 | Taken together, these results indicate that Ang II can regulate the development of mesangial matrix expansion in the early phase of diabetic nephropathy through Src and Smad1. |
| 282 | 16767106 | Angiotensin II-dependent Src and Smad1 signaling pathway is crucial for the development of diabetic nephropathy. |
| 283 | 16767106 | We have reported that Smad1 plays a key role in diabetic mesangial matrix expansion and directly regulates the transcription of type IV collagen (Col4) in vitro and in vivo. |
| 284 | 16767106 | Here we examined the effect of Ang II on the expression of Smad1 and mesangial matrix expansion in streptozotocin (STZ)-induced diabetic rats in vivo, using Ang II type 1 receptor blocker, olmesartan. |
| 285 | 16767106 | Ang II induced Col4 synthesis and increased expression of phospho-Src and phospho-Smad1 in cultured mesangial cells, which was blocked by olmesartan. |
| 286 | 16767106 | Taken together, these results indicate that Ang II can regulate the development of mesangial matrix expansion in the early phase of diabetic nephropathy through Src and Smad1. |
| 287 | 16973905 | APOE4-VLDL inhibits the HDL-activated phosphatidylinositol 3-kinase/Akt Pathway via the phosphoinositol phosphatase SHIP2. |
| 288 | 16973905 | We show that APOE4-VLDL diminishes the phosphorylation of Akt by HDL but does not alter phosphorylation of c-Jun N-terminal kinase, p38, or Src family kinases by HDL. |
| 289 | 16973905 | Furthermore APOE4-VLDL inhibits Akt phosphorylation by reducing the phosphatidylinositol 3-kinase product phosphatidylinositol-(3,4,5)-triphosphate (PI[3,4,5]P3). |
| 290 | 16973905 | Therefore the activation of SHIP2 by APOE4-VLDL, with the subsequent inhibition of the HDL/Akt pathway, is a novel and significant biological mechanism and may be a critical intermediate by which APOE4 increases the risk of atherosclerotic CVD. |
| 291 | 17272398 | Exposure of both murine and human podocytes to GH (50-500 ng/ml) resulted in an increase in abundance of phosphorylated signal transducer and activator of transcription-5, Janus kinase-2, and ERK1/2 proteins. |
| 292 | 17272398 | Exposure of podocytes to GH also caused changes in the intracellular distribution of the Janus kinase-2 adapter protein Src homology 2-Bbeta, stimulation of focal adhesion kinase, increase in reactive oxygen species, and GH-dependent changes in the actin cytoskeleton. |
| 293 | 17306383 | CCK causes PKD1 activation in pancreatic acini by signaling through PKC-delta and PKC-independent pathways. |
| 294 | 17306383 | CCK activated PKD1 and caused a time- and dose-dependent increase in serine phosphorylation by activation of high- and low-affinity CCK(A) receptor states. |
| 295 | 17306383 | Inhibition of CCK-stimulated increases in phospholipase C, PKC activity or intracellular calcium decreased PKD1 S916 phosphorylation by 56%, 62% and 96%, respectively. |
| 296 | 17306383 | Inhibition of Src/PI3K/MAPK/tyrosine phosphorylation had no effect. |
| 297 | 17306383 | These results demonstrate that CCK(A) receptor activation leads to PKD activation by signaling through PKC-dependent and PKC-independent pathways. |
| 298 | 17494630 | These pathways, which may be activated simultaneously or selectively, elevate [Ca(2+)](i), activate Src and the ERK1/2 kinase pathways, and activate phosphoinositide 3-kinase and protein kinase B (Akt), NF-kappaB, and reactive oxygen species. |
| 299 | 17991742 | c-Src is required for tropomyosin receptor kinase C (TrkC)-induced activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway. |
| 300 | 17991742 | TrkC expression leads to the constitutive activation of two major effector pathways, namely the Ras-MAP kinase (MAPK) mitogenic pathway and the phosphatidylinositol 3-kinase (PI3K)-AKT pathway mediating cell survival. |
| 301 | 17991742 | Here we define some aspects of the molecular mechanisms regulating TrkC-dependent Ras-Erk1/2 and PI3K/Akt activation. |
| 302 | 17991742 | We show that endogenous TrkC associated with c-Src in human and mouse cancer cells which express TrkC. |
| 303 | 17991742 | Suppression of c-Src by RNA interference in highly metastatic 4T1 mammary cancer cells, which express endogenous TrkC, resulted in markedly decreased expression of cyclin D1 and suppression of activation of Ras-Erk1/2 and PI3K-Akt. |
| 304 | 17991742 | Furthermore, in c-Src-deficient SYF cells, TrkC failed to activate the PI3K-Atk pathway, but not the Ras-Erk1/2 pathway. |
| 305 | 17991742 | Therefore these data indicate that TrkC induces the PI3K-Akt cascade through the activation of c-Src. |
| 306 | 17991742 | c-Src is required for tropomyosin receptor kinase C (TrkC)-induced activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway. |
| 307 | 17991742 | TrkC expression leads to the constitutive activation of two major effector pathways, namely the Ras-MAP kinase (MAPK) mitogenic pathway and the phosphatidylinositol 3-kinase (PI3K)-AKT pathway mediating cell survival. |
| 308 | 17991742 | Here we define some aspects of the molecular mechanisms regulating TrkC-dependent Ras-Erk1/2 and PI3K/Akt activation. |
| 309 | 17991742 | We show that endogenous TrkC associated with c-Src in human and mouse cancer cells which express TrkC. |
| 310 | 17991742 | Suppression of c-Src by RNA interference in highly metastatic 4T1 mammary cancer cells, which express endogenous TrkC, resulted in markedly decreased expression of cyclin D1 and suppression of activation of Ras-Erk1/2 and PI3K-Akt. |
| 311 | 17991742 | Furthermore, in c-Src-deficient SYF cells, TrkC failed to activate the PI3K-Atk pathway, but not the Ras-Erk1/2 pathway. |
| 312 | 17991742 | Therefore these data indicate that TrkC induces the PI3K-Akt cascade through the activation of c-Src. |
| 313 | 17991742 | c-Src is required for tropomyosin receptor kinase C (TrkC)-induced activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway. |
| 314 | 17991742 | TrkC expression leads to the constitutive activation of two major effector pathways, namely the Ras-MAP kinase (MAPK) mitogenic pathway and the phosphatidylinositol 3-kinase (PI3K)-AKT pathway mediating cell survival. |
| 315 | 17991742 | Here we define some aspects of the molecular mechanisms regulating TrkC-dependent Ras-Erk1/2 and PI3K/Akt activation. |
| 316 | 17991742 | We show that endogenous TrkC associated with c-Src in human and mouse cancer cells which express TrkC. |
| 317 | 17991742 | Suppression of c-Src by RNA interference in highly metastatic 4T1 mammary cancer cells, which express endogenous TrkC, resulted in markedly decreased expression of cyclin D1 and suppression of activation of Ras-Erk1/2 and PI3K-Akt. |
| 318 | 17991742 | Furthermore, in c-Src-deficient SYF cells, TrkC failed to activate the PI3K-Atk pathway, but not the Ras-Erk1/2 pathway. |
| 319 | 17991742 | Therefore these data indicate that TrkC induces the PI3K-Akt cascade through the activation of c-Src. |
| 320 | 17991742 | c-Src is required for tropomyosin receptor kinase C (TrkC)-induced activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway. |
| 321 | 17991742 | TrkC expression leads to the constitutive activation of two major effector pathways, namely the Ras-MAP kinase (MAPK) mitogenic pathway and the phosphatidylinositol 3-kinase (PI3K)-AKT pathway mediating cell survival. |
| 322 | 17991742 | Here we define some aspects of the molecular mechanisms regulating TrkC-dependent Ras-Erk1/2 and PI3K/Akt activation. |
| 323 | 17991742 | We show that endogenous TrkC associated with c-Src in human and mouse cancer cells which express TrkC. |
| 324 | 17991742 | Suppression of c-Src by RNA interference in highly metastatic 4T1 mammary cancer cells, which express endogenous TrkC, resulted in markedly decreased expression of cyclin D1 and suppression of activation of Ras-Erk1/2 and PI3K-Akt. |
| 325 | 17991742 | Furthermore, in c-Src-deficient SYF cells, TrkC failed to activate the PI3K-Atk pathway, but not the Ras-Erk1/2 pathway. |
| 326 | 17991742 | Therefore these data indicate that TrkC induces the PI3K-Akt cascade through the activation of c-Src. |
| 327 | 17991742 | c-Src is required for tropomyosin receptor kinase C (TrkC)-induced activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway. |
| 328 | 17991742 | TrkC expression leads to the constitutive activation of two major effector pathways, namely the Ras-MAP kinase (MAPK) mitogenic pathway and the phosphatidylinositol 3-kinase (PI3K)-AKT pathway mediating cell survival. |
| 329 | 17991742 | Here we define some aspects of the molecular mechanisms regulating TrkC-dependent Ras-Erk1/2 and PI3K/Akt activation. |
| 330 | 17991742 | We show that endogenous TrkC associated with c-Src in human and mouse cancer cells which express TrkC. |
| 331 | 17991742 | Suppression of c-Src by RNA interference in highly metastatic 4T1 mammary cancer cells, which express endogenous TrkC, resulted in markedly decreased expression of cyclin D1 and suppression of activation of Ras-Erk1/2 and PI3K-Akt. |
| 332 | 17991742 | Furthermore, in c-Src-deficient SYF cells, TrkC failed to activate the PI3K-Atk pathway, but not the Ras-Erk1/2 pathway. |
| 333 | 17991742 | Therefore these data indicate that TrkC induces the PI3K-Akt cascade through the activation of c-Src. |
| 334 | 18295448 | Angiotensin II (Ang II)-induced renal injury is partly mediated by growth factors such as VEGF. |
| 335 | 18295448 | We have previously shown that Ang II rapidly increases VEGF protein synthesis in proximal tubular epithelial (MCT) cells by augmenting mRNA translation, which is partly dependent on activation and binding of hnRNP K to 3' untranslated region (UTR) of VEGF mRNA. |
| 336 | 18295448 | Transfection with a PKCdelta siRNA inhibited hnRNP K Ser302 phosphorylation and activation, and reduced Ang II stimulation of VEGF synthesis. |
| 337 | 18295448 | Augmented VEGF expression was associated with increased binding of hnRNP K to VEGF mRNA. c-src and PKCdelta activities and hnRNP K phosphorylation on Ser302 in renal cortex of db/db mice were increased compared to control mice. |
| 338 | 18295448 | We conclude: Ang II-induced VEGF mRNA translation is associated with activation of hnRNP K in MCT cells. |
| 339 | 18295448 | In the signaling pathway leading to hnRNP K activation induced by Ang II, PKCdelta is downstream of c-src. |
| 340 | 18295448 | PKCdelta-mediated phosphorylation of hnRNP K is required for Ang II stimulation of VEGF mRNA translation. |
| 341 | 18295448 | Angiotensin II (Ang II)-induced renal injury is partly mediated by growth factors such as VEGF. |
| 342 | 18295448 | We have previously shown that Ang II rapidly increases VEGF protein synthesis in proximal tubular epithelial (MCT) cells by augmenting mRNA translation, which is partly dependent on activation and binding of hnRNP K to 3' untranslated region (UTR) of VEGF mRNA. |
| 343 | 18295448 | Transfection with a PKCdelta siRNA inhibited hnRNP K Ser302 phosphorylation and activation, and reduced Ang II stimulation of VEGF synthesis. |
| 344 | 18295448 | Augmented VEGF expression was associated with increased binding of hnRNP K to VEGF mRNA. c-src and PKCdelta activities and hnRNP K phosphorylation on Ser302 in renal cortex of db/db mice were increased compared to control mice. |
| 345 | 18295448 | We conclude: Ang II-induced VEGF mRNA translation is associated with activation of hnRNP K in MCT cells. |
| 346 | 18295448 | In the signaling pathway leading to hnRNP K activation induced by Ang II, PKCdelta is downstream of c-src. |
| 347 | 18295448 | PKCdelta-mediated phosphorylation of hnRNP K is required for Ang II stimulation of VEGF mRNA translation. |
| 348 | 18387322 | Platelets from type 2 diabetic patients show an enhanced endogenous reactive oxygen species production and a reduced antioxidant capability, which increase the activity of several tyrosine kinases, such as the Bruton's tyrosine kinase, MAP kinases or proteins of the SRC family. |
| 349 | 18483622 | Retinal vascular permeability suppression by topical application of a novel VEGFR2/Src kinase inhibitor in mice and rabbits. |
| 350 | 18483622 | We have found that vascular leakage following intravitreal administration of VEGF in mice was abolished by systemic or topical delivery of what we believe is a novel VEGFR2/Src kinase inhibitor; this was confirmed in rabbits. |
| 351 | 18483622 | The relevance of Src inhibition to VEGF-associated alterations in vascular permeability was further substantiated by genetic studies in which VEGF injection or laser-induced vascular permeability failed to augment retinal vascular permeability in Src-/- and Yes-/- mice (Src and Yes are ubiquitously expressed Src kinase family members; Src-/- and Yes-/- mice lacking expression of these kinases show no vascular leak in response to VEGF). |
| 352 | 18483622 | Retinal vascular permeability suppression by topical application of a novel VEGFR2/Src kinase inhibitor in mice and rabbits. |
| 353 | 18483622 | We have found that vascular leakage following intravitreal administration of VEGF in mice was abolished by systemic or topical delivery of what we believe is a novel VEGFR2/Src kinase inhibitor; this was confirmed in rabbits. |
| 354 | 18483622 | The relevance of Src inhibition to VEGF-associated alterations in vascular permeability was further substantiated by genetic studies in which VEGF injection or laser-induced vascular permeability failed to augment retinal vascular permeability in Src-/- and Yes-/- mice (Src and Yes are ubiquitously expressed Src kinase family members; Src-/- and Yes-/- mice lacking expression of these kinases show no vascular leak in response to VEGF). |
| 355 | 18483622 | Retinal vascular permeability suppression by topical application of a novel VEGFR2/Src kinase inhibitor in mice and rabbits. |
| 356 | 18483622 | We have found that vascular leakage following intravitreal administration of VEGF in mice was abolished by systemic or topical delivery of what we believe is a novel VEGFR2/Src kinase inhibitor; this was confirmed in rabbits. |
| 357 | 18483622 | The relevance of Src inhibition to VEGF-associated alterations in vascular permeability was further substantiated by genetic studies in which VEGF injection or laser-induced vascular permeability failed to augment retinal vascular permeability in Src-/- and Yes-/- mice (Src and Yes are ubiquitously expressed Src kinase family members; Src-/- and Yes-/- mice lacking expression of these kinases show no vascular leak in response to VEGF). |
| 358 | 18602447 | This process is triggered by hGH-stimulated activation of the non-receptor tyrosine kinases JAK2 and c-Src, which causes tyrosine phosphorylation of RyRs, resulting in sensitization of CICR. |
| 359 | 18602447 | The rise in [Ca(2+)](i) elicited by hGH is associated with an enhanced insulin secretion, effects that are mediated mainly through the prolactin receptor. |
| 360 | 18602447 | These mechanisms indicate that a rise in [Ca(2+)](i) elicited by activation of PRLR is JAK2-dependent and is associated with enhanced insulin secretion. |
| 361 | 18602447 | In contrast, GH receptor-mediated increase in [Ca(2+)](i) is JAK2-independent and is dissociated from insulin secretion. |
| 362 | 18633106 | Integrin-associated protein association with SRC homology 2 domain containing tyrosine phosphatase substrate 1 regulates igf-I signaling in vivo. |
| 363 | 18635660 | Expression of Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 in pancreatic beta-Cells and its role in promotion of insulin secretion and protection against diabetes. |
| 364 | 18635660 | Transmembrane proteins Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 (SHPS-1) and its ligand CD47 interact through their extracellular regions and contribute to intercellular communication. |
| 365 | 18635660 | We now show that both SHPS-1 and CD47 are prominently expressed in beta-cells of the pancreas. |
| 366 | 18635660 | The plasma insulin level in the randomly fed state was markedly reduced in mice that express a mutant form of SHPS-1 lacking most of the cytoplasmic region compared with that in wild-type (WT) mice, although the blood glucose concentrations of the two types of mice were similar. |
| 367 | 18635660 | This reduction in the plasma insulin level of SHPS-1 mutant mice was even more pronounced in animals maintained on a high-fat diet. |
| 368 | 18635660 | Glucose tolerance was also markedly impaired in SHPS-1 mutant mice on a high-fat diet, whereas both peripheral insulin sensitivity and the insulin content of the pancreas in the mutant animals were similar to those of WT mice. |
| 369 | 18635660 | Glucose-stimulated insulin secretion was similar for islets isolated from WT or SHPS-1 mutant mice. |
| 370 | 18635660 | These results suggest that SHPS-1 promotes insulin secretion from beta-cells and thereby protects against diabetes. |
| 371 | 18635660 | Preventing of alpha2-adrenergic receptor-mediated inhibition of insulin secretion may partly participate in such a function of SHPS-1. |
| 372 | 18635660 | Expression of Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 in pancreatic beta-Cells and its role in promotion of insulin secretion and protection against diabetes. |
| 373 | 18635660 | Transmembrane proteins Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 (SHPS-1) and its ligand CD47 interact through their extracellular regions and contribute to intercellular communication. |
| 374 | 18635660 | We now show that both SHPS-1 and CD47 are prominently expressed in beta-cells of the pancreas. |
| 375 | 18635660 | The plasma insulin level in the randomly fed state was markedly reduced in mice that express a mutant form of SHPS-1 lacking most of the cytoplasmic region compared with that in wild-type (WT) mice, although the blood glucose concentrations of the two types of mice were similar. |
| 376 | 18635660 | This reduction in the plasma insulin level of SHPS-1 mutant mice was even more pronounced in animals maintained on a high-fat diet. |
| 377 | 18635660 | Glucose tolerance was also markedly impaired in SHPS-1 mutant mice on a high-fat diet, whereas both peripheral insulin sensitivity and the insulin content of the pancreas in the mutant animals were similar to those of WT mice. |
| 378 | 18635660 | Glucose-stimulated insulin secretion was similar for islets isolated from WT or SHPS-1 mutant mice. |
| 379 | 18635660 | These results suggest that SHPS-1 promotes insulin secretion from beta-cells and thereby protects against diabetes. |
| 380 | 18635660 | Preventing of alpha2-adrenergic receptor-mediated inhibition of insulin secretion may partly participate in such a function of SHPS-1. |
| 381 | 18945941 | High glucose promotes retinal endothelial cell migration through activation of Src, PI3K/Akt1/eNOS, and ERKs. |
| 382 | 18945941 | Retinal EC under high-glucose conditions also expressed increased levels of fibronectin, osteopontin, and alpha(v)beta(3)-integrin, and reduced levels of thrombospondin-1. |
| 383 | 18945941 | These changes were concomitant with sustained activation of the downstream prosurvival and promigratory signaling pathways, including Src kinase, phosphatidylinositol 3-kinase/Akt1/endothelial nitric oxide synthase, and ERKs. |
| 384 | 19122674 | Further investigation reveals that insulin stimulates the formation of a new beta-arrestin-2 signal complex, in which beta-arrestin-2 scaffolds Akt and Src to insulin receptor. |
| 385 | 19135126 | Ang-II-induced Ca(2+) influx was blocked by neither VDCC nor c-src inhibition but was sensitive to inositol 1,4,5-trisphosphate receptor inhibition, lanthanide and the diacylglycerol analogue, oleoyl-2-acetyl-sn-glycerol. |
| 386 | 19230846 | Inhibition of PI3 kinase and Src kinases decreased (p < 0.05) G6PD activity in the fa/fa but not in the lean rat liver, suggesting that G6PD activity is regulated by PI3/Src kinase signaling pathways. |
| 387 | 19230846 | G6PD-derived NADPH increased (p < 0.05) superoxide anion levels by 70-90% in fa/fa vs lean rat liver, which was inhibited by the NADPH oxidase inhibitor gp91(ds-tat) (50 microM) and G6PD inhibitors 6-aminonicotinamide (1 mM) and dehydroepiandrosterone (100 microM), therefore indicating that elevated G6PD activity may be responsible for mediating superoxide generation. |
| 388 | 19230846 | Increased G6PD and NADPH oxidase expression and activity, in young hyperglycemic and hyperinsulinemic rats before the development of diabetes, seems to be a contributing factor in the induction of oxidative stress. |
| 389 | 19272022 | Growth factor or insulin stimulation induces a canonical cascade resulting in the transient phosphorylation of PtdIns(4,5)P(2) by PI3K (phosphoinositide 3-kinase) to form PtdIns(3,4,5)P(3), which is rapidly dephosphorylated either by PTEN (phosphatase and tensin homologue deleted on chromosome 10) back to PtdIns(4,5)P(2), or by the 5-ptases (inositol polyphosphate 5-phosphatases), generating PtdIns(3,4)P(2). |
| 390 | 19272022 | Futhermore, the 5-ptases SHIP [SH2 (Src homology 2)-domain-containing inositol phosphatase] 2, SKIP (skeletal muscle- and kidney-enriched inositol phosphatase) and 72-5ptase (72 kDa 5-ptase)/Type IV/Inpp5e (inositol polyphosphate 5-phosphatase E) are implicated in negatively regulating insulin signalling and glucose homoeostasis in specific tissues. |
| 391 | 19272022 | SHIP2 polymorphisms are associated with a predisposition to insulin resistance. |
| 392 | 19272022 | In addition, 5-ptases such as SHIP1, SHIP2 and 72-5ptase/Type IV/Inpp5e regulate macrophage phagocytosis, and SHIP1 also controls haemopoietic cell proliferation. |
| 393 | 19423845 | C-reactive protein inhibits insulin activation of endothelial nitric oxide synthase via the immunoreceptor tyrosine-based inhibition motif of FcgammaRIIB and SHIP-1. |
| 394 | 19423845 | Insulin promotes the cardiovascular protective functions of the endothelium including NO production by endothelial NO synthase (eNOS), which it stimulates via Akt kinase which phosphorylates eNOS Ser1179. |
| 395 | 19423845 | We previously showed that CRP inhibits eNOS activation by insulin by blunting Ser1179 phosphorylation. |
| 396 | 19423845 | We first show in mice that CRP inhibits insulin-induced eNOS phosphorylation, indicating that these processes are operative in vivo. |
| 397 | 19423845 | In endothelial cells we find that CRP attenuates insulin-induced Akt phosphorylation, and CRP antagonism of eNOS is negated by expression of constitutively active Akt; the inhibitory effect of CRP on Akt is also observed in vivo. |
| 398 | 19423845 | Furthermore, we find that endothelium express SHIP-1 (Src homology 2 domain-containing inositol 5'-phosphatase 1), that CRP induces SHIP-1 stimulatory phosphorylation in endothelium in culture and in vivo, and that SHIP-1 knockdown by small interfering RNA prevents CRP antagonism of insulin-induced eNOS activation. |
| 399 | 19423845 | Thus, CRP inhibits eNOS stimulation by insulin via FcgammaRIIB and its ITIM, SHIP-1 activation, and resulting blunted activation of Akt. |
| 400 | 19423845 | These findings provide mechanistic linkage among CRP, impaired insulin signaling in endothelium, and greater cardiovascular disease risk in type 2 diabetes. |
| 401 | 19455054 | The level of cytochrome c expression and caspase 3 activation was also reduced. |
| 402 | 19455054 | BHE elevated antiapoptotic proteins Bcl-2 and heme oxygenase-1 and stimulated the phosphorylation of survival protein Akt simultaneously decreasing the apoptotic proteins Bax and Src. |
| 403 | 19455054 | In addition, BHE enhanced the protein expression of peroxisome proliferator-activated receptor-gamma, peroxisome proliferator-activated receptor-delta, and Glut-4, probably revealing the antiobese and antidiabetic potential of BHE. |
| 404 | 19926790 | We describe widely applicable, calibrated Förster resonance energy transfer methods that quantify structural and biochemical parameters for interaction of the human estrogen receptor alpha-isoform (ER alpha) with the receptor interacting domains (RIDs) of three cofactors (SRC1, SRC2, SRC3) in living cells. |
| 405 | 20029537 | Role of insulin-like growth factor 1 receptor and c-Src in endothelin-1- and angiotensin II-induced PKB phosphorylation, and hypertrophic and proliferative responses in vascular smooth muscle cells. |
| 406 | 20029537 | Endothelin-1 (ET-1) and angiotensin II (Ang II) are vasoactive peptides believed to contribute to the pathogenesis of vascular abnormalities such as hypertension, atherosclerosis, hypertrophy, and restenosis. |
| 407 | 20029537 | We have demonstrated that insulin-like growth factor type 1 receptor (IGF-1R) plays a role in transducing the effect of H2O2, leading to protein kinase B (PKB) phosphorylation. |
| 408 | 20029537 | Since vasoactive peptides elicit their responses through generation of reactive oxygen species, including H2O2, we investigated whether IGF-1R transactivation plays a similar role in ET-1- and Ang II-induced PKB phosphorylation and hypertrophic responses in vascular smooth muscle cells (VSMC). |
| 409 | 20029537 | AG1024, a specific inhibitor of IGF-1R protein tyrosine kinase (PTK), attenuated both ET-1- and Ang II-induced PKB phosphorylation in a dose-dependent manner. |
| 410 | 20029537 | ET-1 and Ang II treatment also induced the phosphorylation of tyrosine residues in the autophosphorylation sites of IGF-1R, which were blocked by AG1024. |
| 411 | 20029537 | In addition, both ET-1 and Ang II evoked tyrosine phosphorylation of c-Src, a nonreceptor PTK, whereas pharmacological inhibition of c-Src PTK activity by PP2, a specific inhibitor of Src-family tyrosine kinase, significantly reduced PKB phosphorylation as well as tyrosine phosphorylation of IGF-1R induced by the 2 vasoactive peptides. |
| 412 | 20029537 | Furthermore, protein and DNA synthesis enhanced by ET-1 and Ang II were attenuated by AG1024 and PP2. |
| 413 | 20029537 | In conclusion, these data suggest that IGF-1R PTK and c-Src PTK play a critical role in mediating PKB phosphorylation as well as hypertrophic and proliferative responses induced by ET-1 and Ang II in A10 VSMC. |
| 414 | 20029537 | Role of insulin-like growth factor 1 receptor and c-Src in endothelin-1- and angiotensin II-induced PKB phosphorylation, and hypertrophic and proliferative responses in vascular smooth muscle cells. |
| 415 | 20029537 | Endothelin-1 (ET-1) and angiotensin II (Ang II) are vasoactive peptides believed to contribute to the pathogenesis of vascular abnormalities such as hypertension, atherosclerosis, hypertrophy, and restenosis. |
| 416 | 20029537 | We have demonstrated that insulin-like growth factor type 1 receptor (IGF-1R) plays a role in transducing the effect of H2O2, leading to protein kinase B (PKB) phosphorylation. |
| 417 | 20029537 | Since vasoactive peptides elicit their responses through generation of reactive oxygen species, including H2O2, we investigated whether IGF-1R transactivation plays a similar role in ET-1- and Ang II-induced PKB phosphorylation and hypertrophic responses in vascular smooth muscle cells (VSMC). |
| 418 | 20029537 | AG1024, a specific inhibitor of IGF-1R protein tyrosine kinase (PTK), attenuated both ET-1- and Ang II-induced PKB phosphorylation in a dose-dependent manner. |
| 419 | 20029537 | ET-1 and Ang II treatment also induced the phosphorylation of tyrosine residues in the autophosphorylation sites of IGF-1R, which were blocked by AG1024. |
| 420 | 20029537 | In addition, both ET-1 and Ang II evoked tyrosine phosphorylation of c-Src, a nonreceptor PTK, whereas pharmacological inhibition of c-Src PTK activity by PP2, a specific inhibitor of Src-family tyrosine kinase, significantly reduced PKB phosphorylation as well as tyrosine phosphorylation of IGF-1R induced by the 2 vasoactive peptides. |
| 421 | 20029537 | Furthermore, protein and DNA synthesis enhanced by ET-1 and Ang II were attenuated by AG1024 and PP2. |
| 422 | 20029537 | In conclusion, these data suggest that IGF-1R PTK and c-Src PTK play a critical role in mediating PKB phosphorylation as well as hypertrophic and proliferative responses induced by ET-1 and Ang II in A10 VSMC. |
| 423 | 20029537 | Role of insulin-like growth factor 1 receptor and c-Src in endothelin-1- and angiotensin II-induced PKB phosphorylation, and hypertrophic and proliferative responses in vascular smooth muscle cells. |
| 424 | 20029537 | Endothelin-1 (ET-1) and angiotensin II (Ang II) are vasoactive peptides believed to contribute to the pathogenesis of vascular abnormalities such as hypertension, atherosclerosis, hypertrophy, and restenosis. |
| 425 | 20029537 | We have demonstrated that insulin-like growth factor type 1 receptor (IGF-1R) plays a role in transducing the effect of H2O2, leading to protein kinase B (PKB) phosphorylation. |
| 426 | 20029537 | Since vasoactive peptides elicit their responses through generation of reactive oxygen species, including H2O2, we investigated whether IGF-1R transactivation plays a similar role in ET-1- and Ang II-induced PKB phosphorylation and hypertrophic responses in vascular smooth muscle cells (VSMC). |
| 427 | 20029537 | AG1024, a specific inhibitor of IGF-1R protein tyrosine kinase (PTK), attenuated both ET-1- and Ang II-induced PKB phosphorylation in a dose-dependent manner. |
| 428 | 20029537 | ET-1 and Ang II treatment also induced the phosphorylation of tyrosine residues in the autophosphorylation sites of IGF-1R, which were blocked by AG1024. |
| 429 | 20029537 | In addition, both ET-1 and Ang II evoked tyrosine phosphorylation of c-Src, a nonreceptor PTK, whereas pharmacological inhibition of c-Src PTK activity by PP2, a specific inhibitor of Src-family tyrosine kinase, significantly reduced PKB phosphorylation as well as tyrosine phosphorylation of IGF-1R induced by the 2 vasoactive peptides. |
| 430 | 20029537 | Furthermore, protein and DNA synthesis enhanced by ET-1 and Ang II were attenuated by AG1024 and PP2. |
| 431 | 20029537 | In conclusion, these data suggest that IGF-1R PTK and c-Src PTK play a critical role in mediating PKB phosphorylation as well as hypertrophic and proliferative responses induced by ET-1 and Ang II in A10 VSMC. |
| 432 | 20182516 | Functional recovery of diabetic mouse hearts by glutaredoxin-1 gene therapy: role of Akt-FoxO-signaling network. |
| 433 | 20182516 | In concert, Glrx-1 prevented diabetes and ischemia-reperfusion induced reduction of cardioprotective proteins including Akt, FoxO-1, and hemeoxygenase-1, and abolished the death signal triggered by Jnk, p38 mitogen-activated protein kinase, and c-Src. |
| 434 | 20232313 | Mesenchymal transition and concomitant losses in insulin gene expression observed on C-IV were found to be dependent on beta(1)-integrin ligation and were augmented in the presence of hepatocyte growth factor. |
| 435 | 20232313 | Importantly, selective inhibition of c-Src, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) prior to exposure to C-IV prevented mesenchymal transition and effectively preserved insulin expression. |
| 436 | 20232313 | Inhibition of Src-, ERK-, or JNK-dependent signaling combined with the selective regulation of matrix exposure may ultimately facilitate the development of more effective beta-cell expansion protocols. |
| 437 | 20555420 | Involvement of insulin-like growth factor 1 receptor transactivation in endothelin-1-induced signaling in vascular smooth muscle cells. |
| 438 | 20555420 | However, recent studies have implicated insulin-like growth factor 1 receptor transactivation in this process. |
| 439 | 20555420 | In this review, we will examine the contribution of both insulin-like growth factor 1 receptor and c-Src in mediating ET-1-induced signaling responses in vascular smooth muscle cells. |
| 440 | 21506908 | p66Shc, a 66 kDa proto-oncogene Src collagen homologue (Shc) adaptor protein, is classically known as a signalling protein implicated in receptor tyrosine kinase signal transduction. |
| 441 | 21638209 | TGF-β1 → SMAD/p53/USF2 → PAI-1 transcriptional axis in ureteral obstruction-induced renal fibrosis. |
| 442 | 21638209 | SMAD and non-SMAD pathways (pp60(c-src), epidermal growth factor receptor [EGFR], mitogen-activated protein kinase, p53) are required for PAI-1 induction by TGF-β1. |
| 443 | 21638209 | SMAD2/3, pp60(c-src), EGFR, and p53 activation are each increased in the obstructed kidney. |
| 444 | 21638209 | TGF-β1 → SMAD/p53/USF2 → PAI-1 transcriptional axis in ureteral obstruction-induced renal fibrosis. |
| 445 | 21638209 | SMAD and non-SMAD pathways (pp60(c-src), epidermal growth factor receptor [EGFR], mitogen-activated protein kinase, p53) are required for PAI-1 induction by TGF-β1. |
| 446 | 21638209 | SMAD2/3, pp60(c-src), EGFR, and p53 activation are each increased in the obstructed kidney. |
| 447 | 21810446 | Particular attention was paid to cholecystokinin (CCK), a physiological regulator of pancreatic function and important in pathological processes affecting acinar function, like pancreatitis. |
| 448 | 21810446 | PKCθ was activated in time- and dose-related manner by CCK, mediated 30% by high-affinity CCK(A)-receptor activation. |
| 449 | 21810446 | PKCθ inhibition (by pseudostrate-inhibitor or dominant negative) inhibited CCK- and TPA-stimulation of PKD, Src, RafC, PYK2, p125(FAK) and IKKα/β, but not basal/stimulated enzyme secretion. |
| 450 | 21810446 | Also CCK- and TPA-induced PKCθ activation produced an increment in PKCθ's direct association with AKT, RafA, RafC and Lyn. |
| 451 | 21926342 | Losartan improves aortic endothelium-dependent relaxation via proline-rich tyrosine kinase 2/Src/Akt pathway in type 2 diabetic Goto-Kakizaki rats. |
| 452 | 21926342 | We hypothesized that insulin-induced relaxation and the associated proline-rich tyrosine kinase 2 (Pyk2)/Src/Akt pathway would be abnormal in aortas from the Goto-Kakizaki (GK) type 2 diabetic rat, which exhibits hyperglycemia/insulin resistance, and that losartan treatment of such rats (25 mg·kg(-1)·day(-1) for 2 wk) would correct these abnormalities. |
| 453 | 21926342 | Pyk2, Src, and Akt/endothelial nitric oxide synthase (eNOS) signaling-pathway protein levels and activities were assayed mainly by Western blotting and partly by immunohistochemistry. |
| 454 | 21926342 | In GK (vs. age-matched control) aortas, various insulin-stimulated levels [nitric oxide production and the phosphorylations of eNOS at Ser(1177), of Akt at Thr(308), of phosphoinositide-dependent kinase-1 (PDK1) at Ser(241), of Src at Tyr(416), and of Pyk2 at Tyr(579)] were all significantly decreased and unaffected by either Src inhibitor (PP2) or Pyk2 inhibitor (AG17), while the insulin-stimulated levels of insulin receptor substrate (IRS)-1 phosphorylation at Ser(307), total-eNOS, and total-Akt were significantly increased. |
| 455 | 21926342 | The insulin-stimulated phosphorylation levels of Src/PDK1/Akt/eNOS, but not of Pyk2, were decreased by PP2 in control and losartan-treated GK, but not in GK, aortas. |
| 456 | 21926342 | These results suggest that in the GK diabetic aorta increased phospho-IRS-1 (at Ser(307)) and decreased Pyk2/Src activity inhibit insulin-induced stimulation of the PDK/Akt/eNOS pathway. |
| 457 | 21926342 | Losartan improves aortic endothelium-dependent relaxation via proline-rich tyrosine kinase 2/Src/Akt pathway in type 2 diabetic Goto-Kakizaki rats. |
| 458 | 21926342 | We hypothesized that insulin-induced relaxation and the associated proline-rich tyrosine kinase 2 (Pyk2)/Src/Akt pathway would be abnormal in aortas from the Goto-Kakizaki (GK) type 2 diabetic rat, which exhibits hyperglycemia/insulin resistance, and that losartan treatment of such rats (25 mg·kg(-1)·day(-1) for 2 wk) would correct these abnormalities. |
| 459 | 21926342 | Pyk2, Src, and Akt/endothelial nitric oxide synthase (eNOS) signaling-pathway protein levels and activities were assayed mainly by Western blotting and partly by immunohistochemistry. |
| 460 | 21926342 | In GK (vs. age-matched control) aortas, various insulin-stimulated levels [nitric oxide production and the phosphorylations of eNOS at Ser(1177), of Akt at Thr(308), of phosphoinositide-dependent kinase-1 (PDK1) at Ser(241), of Src at Tyr(416), and of Pyk2 at Tyr(579)] were all significantly decreased and unaffected by either Src inhibitor (PP2) or Pyk2 inhibitor (AG17), while the insulin-stimulated levels of insulin receptor substrate (IRS)-1 phosphorylation at Ser(307), total-eNOS, and total-Akt were significantly increased. |
| 461 | 21926342 | The insulin-stimulated phosphorylation levels of Src/PDK1/Akt/eNOS, but not of Pyk2, were decreased by PP2 in control and losartan-treated GK, but not in GK, aortas. |
| 462 | 21926342 | These results suggest that in the GK diabetic aorta increased phospho-IRS-1 (at Ser(307)) and decreased Pyk2/Src activity inhibit insulin-induced stimulation of the PDK/Akt/eNOS pathway. |
| 463 | 21926342 | Losartan improves aortic endothelium-dependent relaxation via proline-rich tyrosine kinase 2/Src/Akt pathway in type 2 diabetic Goto-Kakizaki rats. |
| 464 | 21926342 | We hypothesized that insulin-induced relaxation and the associated proline-rich tyrosine kinase 2 (Pyk2)/Src/Akt pathway would be abnormal in aortas from the Goto-Kakizaki (GK) type 2 diabetic rat, which exhibits hyperglycemia/insulin resistance, and that losartan treatment of such rats (25 mg·kg(-1)·day(-1) for 2 wk) would correct these abnormalities. |
| 465 | 21926342 | Pyk2, Src, and Akt/endothelial nitric oxide synthase (eNOS) signaling-pathway protein levels and activities were assayed mainly by Western blotting and partly by immunohistochemistry. |
| 466 | 21926342 | In GK (vs. age-matched control) aortas, various insulin-stimulated levels [nitric oxide production and the phosphorylations of eNOS at Ser(1177), of Akt at Thr(308), of phosphoinositide-dependent kinase-1 (PDK1) at Ser(241), of Src at Tyr(416), and of Pyk2 at Tyr(579)] were all significantly decreased and unaffected by either Src inhibitor (PP2) or Pyk2 inhibitor (AG17), while the insulin-stimulated levels of insulin receptor substrate (IRS)-1 phosphorylation at Ser(307), total-eNOS, and total-Akt were significantly increased. |
| 467 | 21926342 | The insulin-stimulated phosphorylation levels of Src/PDK1/Akt/eNOS, but not of Pyk2, were decreased by PP2 in control and losartan-treated GK, but not in GK, aortas. |
| 468 | 21926342 | These results suggest that in the GK diabetic aorta increased phospho-IRS-1 (at Ser(307)) and decreased Pyk2/Src activity inhibit insulin-induced stimulation of the PDK/Akt/eNOS pathway. |
| 469 | 21926342 | Losartan improves aortic endothelium-dependent relaxation via proline-rich tyrosine kinase 2/Src/Akt pathway in type 2 diabetic Goto-Kakizaki rats. |
| 470 | 21926342 | We hypothesized that insulin-induced relaxation and the associated proline-rich tyrosine kinase 2 (Pyk2)/Src/Akt pathway would be abnormal in aortas from the Goto-Kakizaki (GK) type 2 diabetic rat, which exhibits hyperglycemia/insulin resistance, and that losartan treatment of such rats (25 mg·kg(-1)·day(-1) for 2 wk) would correct these abnormalities. |
| 471 | 21926342 | Pyk2, Src, and Akt/endothelial nitric oxide synthase (eNOS) signaling-pathway protein levels and activities were assayed mainly by Western blotting and partly by immunohistochemistry. |
| 472 | 21926342 | In GK (vs. age-matched control) aortas, various insulin-stimulated levels [nitric oxide production and the phosphorylations of eNOS at Ser(1177), of Akt at Thr(308), of phosphoinositide-dependent kinase-1 (PDK1) at Ser(241), of Src at Tyr(416), and of Pyk2 at Tyr(579)] were all significantly decreased and unaffected by either Src inhibitor (PP2) or Pyk2 inhibitor (AG17), while the insulin-stimulated levels of insulin receptor substrate (IRS)-1 phosphorylation at Ser(307), total-eNOS, and total-Akt were significantly increased. |
| 473 | 21926342 | The insulin-stimulated phosphorylation levels of Src/PDK1/Akt/eNOS, but not of Pyk2, were decreased by PP2 in control and losartan-treated GK, but not in GK, aortas. |
| 474 | 21926342 | These results suggest that in the GK diabetic aorta increased phospho-IRS-1 (at Ser(307)) and decreased Pyk2/Src activity inhibit insulin-induced stimulation of the PDK/Akt/eNOS pathway. |
| 475 | 21926342 | Losartan improves aortic endothelium-dependent relaxation via proline-rich tyrosine kinase 2/Src/Akt pathway in type 2 diabetic Goto-Kakizaki rats. |
| 476 | 21926342 | We hypothesized that insulin-induced relaxation and the associated proline-rich tyrosine kinase 2 (Pyk2)/Src/Akt pathway would be abnormal in aortas from the Goto-Kakizaki (GK) type 2 diabetic rat, which exhibits hyperglycemia/insulin resistance, and that losartan treatment of such rats (25 mg·kg(-1)·day(-1) for 2 wk) would correct these abnormalities. |
| 477 | 21926342 | Pyk2, Src, and Akt/endothelial nitric oxide synthase (eNOS) signaling-pathway protein levels and activities were assayed mainly by Western blotting and partly by immunohistochemistry. |
| 478 | 21926342 | In GK (vs. age-matched control) aortas, various insulin-stimulated levels [nitric oxide production and the phosphorylations of eNOS at Ser(1177), of Akt at Thr(308), of phosphoinositide-dependent kinase-1 (PDK1) at Ser(241), of Src at Tyr(416), and of Pyk2 at Tyr(579)] were all significantly decreased and unaffected by either Src inhibitor (PP2) or Pyk2 inhibitor (AG17), while the insulin-stimulated levels of insulin receptor substrate (IRS)-1 phosphorylation at Ser(307), total-eNOS, and total-Akt were significantly increased. |
| 479 | 21926342 | The insulin-stimulated phosphorylation levels of Src/PDK1/Akt/eNOS, but not of Pyk2, were decreased by PP2 in control and losartan-treated GK, but not in GK, aortas. |
| 480 | 21926342 | These results suggest that in the GK diabetic aorta increased phospho-IRS-1 (at Ser(307)) and decreased Pyk2/Src activity inhibit insulin-induced stimulation of the PDK/Akt/eNOS pathway. |
| 481 | 21966580 | These include phosphorylation/arrestin-dependent activation of protein kinase D1, Src family kinase-dependent activation of the sodium channel NALCN and the involvement of regulator of G protein signaling (RGS)-4. |
| 482 | 22148072 | Hyperglycemia enhances IGF-I-stimulated Src activation via increasing Nox4-derived reactive oxygen species in a PKCζ-dependent manner in vascular smooth muscle cells. |
| 483 | 22148072 | The aim of the current study was to determine the mechanism by which hyperglycemia enhances IGF-I-stimulated Src activation and the role of NADPH oxidase 4 (Nox4) and protein kinase C ζ (PKCζ) in mediating this response in vascular smooth muscle cells (VSMCs). |
| 484 | 22148072 | The role of Nox4-derived reactive oxygen species (ROS) in IGF-I-stimulated Src activation was investigated via knockdown of Nox4. |
| 485 | 22148072 | Hyperglycemia induced Nox4, but not Nox1, and p22 phagocyte oxidase (p22phox) expression and IGF-I stimulated Nox4/p22phox complex formation, leading to increased ROS generation. |
| 486 | 22148072 | Knockdown of Nox4 prevented ROS generation and impaired the oxidation and activation of Src in response to IGF-I, whereas knockdown of Nox1 had no effect. |
| 487 | 22148072 | Nox4-derived ROS is responsible for the enhancing effect of hyperglycemia on IGF-I-stimulated Src activation, which in turn amplifies IGF-I-linked downstream signaling and biological actions. |
| 488 | 22148072 | Hyperglycemia enhances IGF-I-stimulated Src activation via increasing Nox4-derived reactive oxygen species in a PKCζ-dependent manner in vascular smooth muscle cells. |
| 489 | 22148072 | The aim of the current study was to determine the mechanism by which hyperglycemia enhances IGF-I-stimulated Src activation and the role of NADPH oxidase 4 (Nox4) and protein kinase C ζ (PKCζ) in mediating this response in vascular smooth muscle cells (VSMCs). |
| 490 | 22148072 | The role of Nox4-derived reactive oxygen species (ROS) in IGF-I-stimulated Src activation was investigated via knockdown of Nox4. |
| 491 | 22148072 | Hyperglycemia induced Nox4, but not Nox1, and p22 phagocyte oxidase (p22phox) expression and IGF-I stimulated Nox4/p22phox complex formation, leading to increased ROS generation. |
| 492 | 22148072 | Knockdown of Nox4 prevented ROS generation and impaired the oxidation and activation of Src in response to IGF-I, whereas knockdown of Nox1 had no effect. |
| 493 | 22148072 | Nox4-derived ROS is responsible for the enhancing effect of hyperglycemia on IGF-I-stimulated Src activation, which in turn amplifies IGF-I-linked downstream signaling and biological actions. |
| 494 | 22148072 | Hyperglycemia enhances IGF-I-stimulated Src activation via increasing Nox4-derived reactive oxygen species in a PKCζ-dependent manner in vascular smooth muscle cells. |
| 495 | 22148072 | The aim of the current study was to determine the mechanism by which hyperglycemia enhances IGF-I-stimulated Src activation and the role of NADPH oxidase 4 (Nox4) and protein kinase C ζ (PKCζ) in mediating this response in vascular smooth muscle cells (VSMCs). |
| 496 | 22148072 | The role of Nox4-derived reactive oxygen species (ROS) in IGF-I-stimulated Src activation was investigated via knockdown of Nox4. |
| 497 | 22148072 | Hyperglycemia induced Nox4, but not Nox1, and p22 phagocyte oxidase (p22phox) expression and IGF-I stimulated Nox4/p22phox complex formation, leading to increased ROS generation. |
| 498 | 22148072 | Knockdown of Nox4 prevented ROS generation and impaired the oxidation and activation of Src in response to IGF-I, whereas knockdown of Nox1 had no effect. |
| 499 | 22148072 | Nox4-derived ROS is responsible for the enhancing effect of hyperglycemia on IGF-I-stimulated Src activation, which in turn amplifies IGF-I-linked downstream signaling and biological actions. |
| 500 | 22148072 | Hyperglycemia enhances IGF-I-stimulated Src activation via increasing Nox4-derived reactive oxygen species in a PKCζ-dependent manner in vascular smooth muscle cells. |
| 501 | 22148072 | The aim of the current study was to determine the mechanism by which hyperglycemia enhances IGF-I-stimulated Src activation and the role of NADPH oxidase 4 (Nox4) and protein kinase C ζ (PKCζ) in mediating this response in vascular smooth muscle cells (VSMCs). |
| 502 | 22148072 | The role of Nox4-derived reactive oxygen species (ROS) in IGF-I-stimulated Src activation was investigated via knockdown of Nox4. |
| 503 | 22148072 | Hyperglycemia induced Nox4, but not Nox1, and p22 phagocyte oxidase (p22phox) expression and IGF-I stimulated Nox4/p22phox complex formation, leading to increased ROS generation. |
| 504 | 22148072 | Knockdown of Nox4 prevented ROS generation and impaired the oxidation and activation of Src in response to IGF-I, whereas knockdown of Nox1 had no effect. |
| 505 | 22148072 | Nox4-derived ROS is responsible for the enhancing effect of hyperglycemia on IGF-I-stimulated Src activation, which in turn amplifies IGF-I-linked downstream signaling and biological actions. |
| 506 | 22148072 | Hyperglycemia enhances IGF-I-stimulated Src activation via increasing Nox4-derived reactive oxygen species in a PKCζ-dependent manner in vascular smooth muscle cells. |
| 507 | 22148072 | The aim of the current study was to determine the mechanism by which hyperglycemia enhances IGF-I-stimulated Src activation and the role of NADPH oxidase 4 (Nox4) and protein kinase C ζ (PKCζ) in mediating this response in vascular smooth muscle cells (VSMCs). |
| 508 | 22148072 | The role of Nox4-derived reactive oxygen species (ROS) in IGF-I-stimulated Src activation was investigated via knockdown of Nox4. |
| 509 | 22148072 | Hyperglycemia induced Nox4, but not Nox1, and p22 phagocyte oxidase (p22phox) expression and IGF-I stimulated Nox4/p22phox complex formation, leading to increased ROS generation. |
| 510 | 22148072 | Knockdown of Nox4 prevented ROS generation and impaired the oxidation and activation of Src in response to IGF-I, whereas knockdown of Nox1 had no effect. |
| 511 | 22148072 | Nox4-derived ROS is responsible for the enhancing effect of hyperglycemia on IGF-I-stimulated Src activation, which in turn amplifies IGF-I-linked downstream signaling and biological actions. |
| 512 | 22403298 | Increased VEGF-dependent angiogenic function in BMECs is mediated by peroxynitrite and involves c-src and MT1-MMP activation. |
| 513 | 22426112 | LYP inhibits T-cell activation when dissociated from CSK. |
| 514 | 22426112 | Lymphoid tyrosine phosphatase (LYP) and C-terminal Src kinase (CSK) are negative regulators of signaling mediated through the T-cell antigen receptor (TCR) and are thought to act in a cooperative manner when forming a complex. |
| 515 | 22426112 | Development of a potent and selective chemical probe of LYP confirmed that LYP inhibits T-cell activation when removed from CSK. |
| 516 | 22426112 | Our findings may explain the reduced TCR-mediated signaling associated with a single-nucleotide polymorphism that confers increased risk for certain autoimmune diseases, including type 1 diabetes and rheumatoid arthritis, and results in expression of a mutant LYP that is unable to bind CSK. |
| 517 | 22886693 | Endothelial hyperpermeability is increased by actomyosin contractile activity in response to phosphorylation of myosin light chain by myosin light chain kinase (MLCK). |
| 518 | 22886693 | MLCK-dependent endothelial hyperpermeability occurs in response to inflammatory mediators (e.g., activated neutrophils, thrombin, histamine, tumor necrosis factor alpha, etc.), through multiple cell signaling pathways and signaling molecules (e.g., Ca(++) , protein kinase C, Src kinase, nitric oxide synthase, etc.). |
| 519 | 22927051 | B. pseudomallei-induced NET formation required NADPH oxidase activation but not phosphatidylinositol-3 kinase, mitogen-activated protein kinases, or Src family kinase signaling pathways. |
| 520 | 22939843 | β-Arrestin1-mediated recruitment of c-Src underlies the proliferative action of glucagon-like peptide-1 in pancreatic β INS832/13 cells. |
| 521 | 22939843 | In the present study, we sought to test the hypothesis that β-arrestin-mediated recruitment of c-Src underlies the proliferative action of GLP-1 in β-cells. |
| 522 | 22939843 | Our results show that GLP-1 increased c-Src phosphorylation in INS832/13 cells, an effect inhibited by siRNA-mediated β-arrestin1 knockdown. |
| 523 | 22939843 | Co-immunoprecipitation experiments showed a physical association between c-Src and both β-arrestin1 and GLP-1R upon GLP-1 treatment. |
| 524 | 22939843 | We propose that the formation of a signaling complex comprising the agonist-stimulated GLP-1R, β-arrestin1 and c-Src is required for the action of GLP-1 on β-cell mass. |
| 525 | 22939843 | β-Arrestin1-mediated recruitment of c-Src underlies the proliferative action of glucagon-like peptide-1 in pancreatic β INS832/13 cells. |
| 526 | 22939843 | In the present study, we sought to test the hypothesis that β-arrestin-mediated recruitment of c-Src underlies the proliferative action of GLP-1 in β-cells. |
| 527 | 22939843 | Our results show that GLP-1 increased c-Src phosphorylation in INS832/13 cells, an effect inhibited by siRNA-mediated β-arrestin1 knockdown. |
| 528 | 22939843 | Co-immunoprecipitation experiments showed a physical association between c-Src and both β-arrestin1 and GLP-1R upon GLP-1 treatment. |
| 529 | 22939843 | We propose that the formation of a signaling complex comprising the agonist-stimulated GLP-1R, β-arrestin1 and c-Src is required for the action of GLP-1 on β-cell mass. |
| 530 | 22939843 | β-Arrestin1-mediated recruitment of c-Src underlies the proliferative action of glucagon-like peptide-1 in pancreatic β INS832/13 cells. |
| 531 | 22939843 | In the present study, we sought to test the hypothesis that β-arrestin-mediated recruitment of c-Src underlies the proliferative action of GLP-1 in β-cells. |
| 532 | 22939843 | Our results show that GLP-1 increased c-Src phosphorylation in INS832/13 cells, an effect inhibited by siRNA-mediated β-arrestin1 knockdown. |
| 533 | 22939843 | Co-immunoprecipitation experiments showed a physical association between c-Src and both β-arrestin1 and GLP-1R upon GLP-1 treatment. |
| 534 | 22939843 | We propose that the formation of a signaling complex comprising the agonist-stimulated GLP-1R, β-arrestin1 and c-Src is required for the action of GLP-1 on β-cell mass. |
| 535 | 22939843 | β-Arrestin1-mediated recruitment of c-Src underlies the proliferative action of glucagon-like peptide-1 in pancreatic β INS832/13 cells. |
| 536 | 22939843 | In the present study, we sought to test the hypothesis that β-arrestin-mediated recruitment of c-Src underlies the proliferative action of GLP-1 in β-cells. |
| 537 | 22939843 | Our results show that GLP-1 increased c-Src phosphorylation in INS832/13 cells, an effect inhibited by siRNA-mediated β-arrestin1 knockdown. |
| 538 | 22939843 | Co-immunoprecipitation experiments showed a physical association between c-Src and both β-arrestin1 and GLP-1R upon GLP-1 treatment. |
| 539 | 22939843 | We propose that the formation of a signaling complex comprising the agonist-stimulated GLP-1R, β-arrestin1 and c-Src is required for the action of GLP-1 on β-cell mass. |
| 540 | 22939843 | β-Arrestin1-mediated recruitment of c-Src underlies the proliferative action of glucagon-like peptide-1 in pancreatic β INS832/13 cells. |
| 541 | 22939843 | In the present study, we sought to test the hypothesis that β-arrestin-mediated recruitment of c-Src underlies the proliferative action of GLP-1 in β-cells. |
| 542 | 22939843 | Our results show that GLP-1 increased c-Src phosphorylation in INS832/13 cells, an effect inhibited by siRNA-mediated β-arrestin1 knockdown. |
| 543 | 22939843 | Co-immunoprecipitation experiments showed a physical association between c-Src and both β-arrestin1 and GLP-1R upon GLP-1 treatment. |
| 544 | 22939843 | We propose that the formation of a signaling complex comprising the agonist-stimulated GLP-1R, β-arrestin1 and c-Src is required for the action of GLP-1 on β-cell mass. |
| 545 | 22982565 | Amurensin G enhanced the activities of phosphatidylinositol 3-kinase (PI3K) and Src and their chemical inhibitors suppressed amurensin G-stimulated eNOS phosphorylation. |
| 546 | 22982565 | Moreover, amurensin G activated AMP-activated protein kinase (AMPK), and amurensin G-stimulated eNOS phosphorylation and PI3K activation were reversed by AMPK inhibition. |
| 547 | 22982565 | ER inhibition reversed AMPK-dependent PI3K activation in response to amurensin G. |
| 548 | 22982565 | Amurensin G-mediated endothelium-dependent relaxation was blocked by inhibition of AMPK, ER, Src, or PI3K. |
| 549 | 22982565 | These results suggest that amurensin G enhances NO production via eNOS phosphorylation in endothelial cells, and ER-dependent AMPK/PI3K pathways are required. |
| 550 | 22982565 | Amurensin G enhanced the activities of phosphatidylinositol 3-kinase (PI3K) and Src and their chemical inhibitors suppressed amurensin G-stimulated eNOS phosphorylation. |
| 551 | 22982565 | Moreover, amurensin G activated AMP-activated protein kinase (AMPK), and amurensin G-stimulated eNOS phosphorylation and PI3K activation were reversed by AMPK inhibition. |
| 552 | 22982565 | ER inhibition reversed AMPK-dependent PI3K activation in response to amurensin G. |
| 553 | 22982565 | Amurensin G-mediated endothelium-dependent relaxation was blocked by inhibition of AMPK, ER, Src, or PI3K. |
| 554 | 22982565 | These results suggest that amurensin G enhances NO production via eNOS phosphorylation in endothelial cells, and ER-dependent AMPK/PI3K pathways are required. |
| 555 | 23364683 | The in vitro assay showed that HPN exhibited enhanced inhibitory activity against PTP1B with IC(50) 0.63 μmol/L and high selectivity against other PTPs (T cell protein tyrosine phosphatase (TCPTP), leucocyte antigen-related tyrosine phosphatase (LAR), Src homology 2-containing protein tyrosine phosphatase-1 (SHP-1) and SHP-2). |
| 556 | 23364683 | Western blotting results showed that HPN decreased PTP1B levels in pancreatic tissue. |
| 557 | 23404499 | In investigating the associated mechanisms, we found that leucine itself does not activate the classical Akt- or ERK1/2 MAP kinase-dependent signaling pathways but can facilitate the insulin-induced phosphorylations of Akt(473) and ERK1/2 in a time- and dose-dependent manner in cultured hepatocytes. |
| 558 | 23404499 | The leucine-facilitated insulin-induced phosphorylation of Akt at residue 473 was not affected by knocking down the key component of mTORC1 or -2 complexes but was blocked by inhibition of c-Src (PP2), PI3K (LY294002), Gαi protein (pertussis toxin or siRNA against Gαi1 gene, or β-arrestin 2 (siRNA)). |
| 559 | 23404499 | Similarly, the leucine-facilitated insulin activation of ERK1/2 was also blunted by pertussis toxin. |
| 560 | 23472139 | Activation of Akt by advanced glycation end products (AGEs): involvement of IGF-1 receptor and caveolin-1. |
| 561 | 23472139 | AGEs activate signaling proteins such as Src, Akt and ERK1/2. |
| 562 | 23472139 | The AGEs-stimulated Akt activation was blocked by a PI3-kinase inhibitor LY 294002, Src inhibitor PP2, an antioxidant NAC, superoxide scavenger Tiron, or nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase inhibitor DPI, suggesting the involvement of Src and NAD(P)H oxidase in the activation of PI3-kinase-Akt pathway by AGEs. |
| 563 | 23472139 | The AGEs-stimulated Akt activity was sensitive to Insulin-like growth factor 1 receptor (IGF-1R) kinase inhibitor AG1024. |
| 564 | 23472139 | Furthermore, AGEs induced phosphorylation of IGF-1 receptorβsubunit (IGF-1Rβ) on Tyr1135/1136, which was sensitive to PP2, indicating that AGEs stimulate Akt activity by transactivating IGF-1 receptor. |
| 565 | 23472139 | In addition, the AGEs-stimulated Akt activation was attenuated by β-methylcyclodextrin that abolishes the structure of caveolae, and by lowering caveolin-1 (Cav-1) levels with siRNAs. |
| 566 | 23472139 | Furthermore, addition of AGEs enhanced the interaction of phospho-Cav-1 with IGF-1Rβ and transfection of 3T3-L1 cells with Cav-1 Y14F mutants inhibited the activation of Akt by AGEs. |
| 567 | 23472139 | These results suggest that AGEs activate NAD(P)H oxidase and Src which in turn phosphorylates IGF-1 receptor and Cav-1 leading to activation of IGF-1 receptor and the downstream Akt in 3T3-L1 cells. |
| 568 | 23472139 | AGEs treatment promoted the differentiation of 3T3-L1 preadipocytes and addition of AG1024, LY 294002 or Akt inhibitor attenuated the promoting effect of AGEs on adipogenesis, suggesting that IGF-1 receptor, PI3-Kinase and Akt are involved in the facilitation of adipogenesis by AGEs. |
| 569 | 23472139 | Activation of Akt by advanced glycation end products (AGEs): involvement of IGF-1 receptor and caveolin-1. |
| 570 | 23472139 | AGEs activate signaling proteins such as Src, Akt and ERK1/2. |
| 571 | 23472139 | The AGEs-stimulated Akt activation was blocked by a PI3-kinase inhibitor LY 294002, Src inhibitor PP2, an antioxidant NAC, superoxide scavenger Tiron, or nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase inhibitor DPI, suggesting the involvement of Src and NAD(P)H oxidase in the activation of PI3-kinase-Akt pathway by AGEs. |
| 572 | 23472139 | The AGEs-stimulated Akt activity was sensitive to Insulin-like growth factor 1 receptor (IGF-1R) kinase inhibitor AG1024. |
| 573 | 23472139 | Furthermore, AGEs induced phosphorylation of IGF-1 receptorβsubunit (IGF-1Rβ) on Tyr1135/1136, which was sensitive to PP2, indicating that AGEs stimulate Akt activity by transactivating IGF-1 receptor. |
| 574 | 23472139 | In addition, the AGEs-stimulated Akt activation was attenuated by β-methylcyclodextrin that abolishes the structure of caveolae, and by lowering caveolin-1 (Cav-1) levels with siRNAs. |
| 575 | 23472139 | Furthermore, addition of AGEs enhanced the interaction of phospho-Cav-1 with IGF-1Rβ and transfection of 3T3-L1 cells with Cav-1 Y14F mutants inhibited the activation of Akt by AGEs. |
| 576 | 23472139 | These results suggest that AGEs activate NAD(P)H oxidase and Src which in turn phosphorylates IGF-1 receptor and Cav-1 leading to activation of IGF-1 receptor and the downstream Akt in 3T3-L1 cells. |
| 577 | 23472139 | AGEs treatment promoted the differentiation of 3T3-L1 preadipocytes and addition of AG1024, LY 294002 or Akt inhibitor attenuated the promoting effect of AGEs on adipogenesis, suggesting that IGF-1 receptor, PI3-Kinase and Akt are involved in the facilitation of adipogenesis by AGEs. |
| 578 | 23472139 | Activation of Akt by advanced glycation end products (AGEs): involvement of IGF-1 receptor and caveolin-1. |
| 579 | 23472139 | AGEs activate signaling proteins such as Src, Akt and ERK1/2. |
| 580 | 23472139 | The AGEs-stimulated Akt activation was blocked by a PI3-kinase inhibitor LY 294002, Src inhibitor PP2, an antioxidant NAC, superoxide scavenger Tiron, or nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase inhibitor DPI, suggesting the involvement of Src and NAD(P)H oxidase in the activation of PI3-kinase-Akt pathway by AGEs. |
| 581 | 23472139 | The AGEs-stimulated Akt activity was sensitive to Insulin-like growth factor 1 receptor (IGF-1R) kinase inhibitor AG1024. |
| 582 | 23472139 | Furthermore, AGEs induced phosphorylation of IGF-1 receptorβsubunit (IGF-1Rβ) on Tyr1135/1136, which was sensitive to PP2, indicating that AGEs stimulate Akt activity by transactivating IGF-1 receptor. |
| 583 | 23472139 | In addition, the AGEs-stimulated Akt activation was attenuated by β-methylcyclodextrin that abolishes the structure of caveolae, and by lowering caveolin-1 (Cav-1) levels with siRNAs. |
| 584 | 23472139 | Furthermore, addition of AGEs enhanced the interaction of phospho-Cav-1 with IGF-1Rβ and transfection of 3T3-L1 cells with Cav-1 Y14F mutants inhibited the activation of Akt by AGEs. |
| 585 | 23472139 | These results suggest that AGEs activate NAD(P)H oxidase and Src which in turn phosphorylates IGF-1 receptor and Cav-1 leading to activation of IGF-1 receptor and the downstream Akt in 3T3-L1 cells. |
| 586 | 23472139 | AGEs treatment promoted the differentiation of 3T3-L1 preadipocytes and addition of AG1024, LY 294002 or Akt inhibitor attenuated the promoting effect of AGEs on adipogenesis, suggesting that IGF-1 receptor, PI3-Kinase and Akt are involved in the facilitation of adipogenesis by AGEs. |
| 587 | 23526543 | Next, data obtained with selective pharmacological inhibitors and small interfering RNAs (siRNAs) showed that HG-induced MMP-9 expression is mediated through a c-Src-dependent reactive oxygen species (ROS) signal linking to activation of mitogen-activated protein kinases (MAPKs). |
| 588 | 23526543 | Subsequently, the transcriptional factor nuclear factor-kappa B (NF-κB) was activated and thereby turned on transcription of MMP-9 gene. |
| 589 | 23565109 | First, regulation of cytokine-stimulated NOX-1 expression has been linked to inflammatory lipid mediators derived from 12-lipoxygenase activity. |
| 590 | 23565109 | Second, regulation of NOX-1 in beta cells involves feed-forward control linked to elevated ROS and Src-kinase activation. |
| 591 | 23612968 | Recruitment of Nox4 to a plasma membrane scaffold is required for localized reactive oxygen species generation and sustained Src activation in response to insulin-like growth factor-I. |
| 592 | 23612968 | Nox4-derived ROS is increased in response to hyperglycemia and is required for IGF-I-stimulated Src activation. |
| 593 | 23612968 | This study was undertaken to determine the mechanism by which Nox4 mediates sustained Src activation. |
| 594 | 23612968 | IGF-I stimulated sustained Src activation, which occurred primarily on the SHPS-1 scaffold protein. |
| 595 | 23612968 | In vitro oxidation experiments indicated that Nox4-derived ROS was able to oxidize Src when they are in close proximity, and Src oxidation leads to its activation. |
| 596 | 23612968 | Therefore we hypothesized that Nox4 recruitment to the plasma membrane scaffold SHPS-1 allowed localized ROS generation to mediate sustained Src oxidation and activation. |
| 597 | 23612968 | To determine the mechanism of Nox4 recruitment, we analyzed the role of Grb2, a component of the SHPS-1 signaling complex. |
| 598 | 23612968 | We determined that Nox4 Tyr-491 was phosphorylated after IGF-I stimulation and was responsible for Nox4 binding to the SH2 domain of Grb2. |
| 599 | 23612968 | Overexpression of a Nox4 mutant, Y491F, prevented Nox4/Grb2 association. |
| 600 | 23612968 | Importantly, it also prevented Nox4 recruitment to SHPS-1. |
| 601 | 23612968 | The role of Grb2 was confirmed using a Pyk2 Y881F mutant, which blocked Grb2 recruitment to SHPS-1. |
| 602 | 23612968 | Cells expressing this mutant had impaired Nox4 recruitment to SHPS-1. |
| 603 | 23612968 | IGF-I-stimulated downstream signaling and biological actions were also significantly impaired in Nox4 Y491F-overexpressing cells. |
| 604 | 23612968 | Disruption of Nox4 recruitment to SHPS-1 in aorta from diabetic mice inhibited IGF-I-stimulated Src oxidation and activation as well as cell proliferation. |
| 605 | 23612968 | Recruitment of Nox4 to a plasma membrane scaffold is required for localized reactive oxygen species generation and sustained Src activation in response to insulin-like growth factor-I. |
| 606 | 23612968 | Nox4-derived ROS is increased in response to hyperglycemia and is required for IGF-I-stimulated Src activation. |
| 607 | 23612968 | This study was undertaken to determine the mechanism by which Nox4 mediates sustained Src activation. |
| 608 | 23612968 | IGF-I stimulated sustained Src activation, which occurred primarily on the SHPS-1 scaffold protein. |
| 609 | 23612968 | In vitro oxidation experiments indicated that Nox4-derived ROS was able to oxidize Src when they are in close proximity, and Src oxidation leads to its activation. |
| 610 | 23612968 | Therefore we hypothesized that Nox4 recruitment to the plasma membrane scaffold SHPS-1 allowed localized ROS generation to mediate sustained Src oxidation and activation. |
| 611 | 23612968 | To determine the mechanism of Nox4 recruitment, we analyzed the role of Grb2, a component of the SHPS-1 signaling complex. |
| 612 | 23612968 | We determined that Nox4 Tyr-491 was phosphorylated after IGF-I stimulation and was responsible for Nox4 binding to the SH2 domain of Grb2. |
| 613 | 23612968 | Overexpression of a Nox4 mutant, Y491F, prevented Nox4/Grb2 association. |
| 614 | 23612968 | Importantly, it also prevented Nox4 recruitment to SHPS-1. |
| 615 | 23612968 | The role of Grb2 was confirmed using a Pyk2 Y881F mutant, which blocked Grb2 recruitment to SHPS-1. |
| 616 | 23612968 | Cells expressing this mutant had impaired Nox4 recruitment to SHPS-1. |
| 617 | 23612968 | IGF-I-stimulated downstream signaling and biological actions were also significantly impaired in Nox4 Y491F-overexpressing cells. |
| 618 | 23612968 | Disruption of Nox4 recruitment to SHPS-1 in aorta from diabetic mice inhibited IGF-I-stimulated Src oxidation and activation as well as cell proliferation. |
| 619 | 23612968 | Recruitment of Nox4 to a plasma membrane scaffold is required for localized reactive oxygen species generation and sustained Src activation in response to insulin-like growth factor-I. |
| 620 | 23612968 | Nox4-derived ROS is increased in response to hyperglycemia and is required for IGF-I-stimulated Src activation. |
| 621 | 23612968 | This study was undertaken to determine the mechanism by which Nox4 mediates sustained Src activation. |
| 622 | 23612968 | IGF-I stimulated sustained Src activation, which occurred primarily on the SHPS-1 scaffold protein. |
| 623 | 23612968 | In vitro oxidation experiments indicated that Nox4-derived ROS was able to oxidize Src when they are in close proximity, and Src oxidation leads to its activation. |
| 624 | 23612968 | Therefore we hypothesized that Nox4 recruitment to the plasma membrane scaffold SHPS-1 allowed localized ROS generation to mediate sustained Src oxidation and activation. |
| 625 | 23612968 | To determine the mechanism of Nox4 recruitment, we analyzed the role of Grb2, a component of the SHPS-1 signaling complex. |
| 626 | 23612968 | We determined that Nox4 Tyr-491 was phosphorylated after IGF-I stimulation and was responsible for Nox4 binding to the SH2 domain of Grb2. |
| 627 | 23612968 | Overexpression of a Nox4 mutant, Y491F, prevented Nox4/Grb2 association. |
| 628 | 23612968 | Importantly, it also prevented Nox4 recruitment to SHPS-1. |
| 629 | 23612968 | The role of Grb2 was confirmed using a Pyk2 Y881F mutant, which blocked Grb2 recruitment to SHPS-1. |
| 630 | 23612968 | Cells expressing this mutant had impaired Nox4 recruitment to SHPS-1. |
| 631 | 23612968 | IGF-I-stimulated downstream signaling and biological actions were also significantly impaired in Nox4 Y491F-overexpressing cells. |
| 632 | 23612968 | Disruption of Nox4 recruitment to SHPS-1 in aorta from diabetic mice inhibited IGF-I-stimulated Src oxidation and activation as well as cell proliferation. |
| 633 | 23612968 | Recruitment of Nox4 to a plasma membrane scaffold is required for localized reactive oxygen species generation and sustained Src activation in response to insulin-like growth factor-I. |
| 634 | 23612968 | Nox4-derived ROS is increased in response to hyperglycemia and is required for IGF-I-stimulated Src activation. |
| 635 | 23612968 | This study was undertaken to determine the mechanism by which Nox4 mediates sustained Src activation. |
| 636 | 23612968 | IGF-I stimulated sustained Src activation, which occurred primarily on the SHPS-1 scaffold protein. |
| 637 | 23612968 | In vitro oxidation experiments indicated that Nox4-derived ROS was able to oxidize Src when they are in close proximity, and Src oxidation leads to its activation. |
| 638 | 23612968 | Therefore we hypothesized that Nox4 recruitment to the plasma membrane scaffold SHPS-1 allowed localized ROS generation to mediate sustained Src oxidation and activation. |
| 639 | 23612968 | To determine the mechanism of Nox4 recruitment, we analyzed the role of Grb2, a component of the SHPS-1 signaling complex. |
| 640 | 23612968 | We determined that Nox4 Tyr-491 was phosphorylated after IGF-I stimulation and was responsible for Nox4 binding to the SH2 domain of Grb2. |
| 641 | 23612968 | Overexpression of a Nox4 mutant, Y491F, prevented Nox4/Grb2 association. |
| 642 | 23612968 | Importantly, it also prevented Nox4 recruitment to SHPS-1. |
| 643 | 23612968 | The role of Grb2 was confirmed using a Pyk2 Y881F mutant, which blocked Grb2 recruitment to SHPS-1. |
| 644 | 23612968 | Cells expressing this mutant had impaired Nox4 recruitment to SHPS-1. |
| 645 | 23612968 | IGF-I-stimulated downstream signaling and biological actions were also significantly impaired in Nox4 Y491F-overexpressing cells. |
| 646 | 23612968 | Disruption of Nox4 recruitment to SHPS-1 in aorta from diabetic mice inhibited IGF-I-stimulated Src oxidation and activation as well as cell proliferation. |
| 647 | 23612968 | Recruitment of Nox4 to a plasma membrane scaffold is required for localized reactive oxygen species generation and sustained Src activation in response to insulin-like growth factor-I. |
| 648 | 23612968 | Nox4-derived ROS is increased in response to hyperglycemia and is required for IGF-I-stimulated Src activation. |
| 649 | 23612968 | This study was undertaken to determine the mechanism by which Nox4 mediates sustained Src activation. |
| 650 | 23612968 | IGF-I stimulated sustained Src activation, which occurred primarily on the SHPS-1 scaffold protein. |
| 651 | 23612968 | In vitro oxidation experiments indicated that Nox4-derived ROS was able to oxidize Src when they are in close proximity, and Src oxidation leads to its activation. |
| 652 | 23612968 | Therefore we hypothesized that Nox4 recruitment to the plasma membrane scaffold SHPS-1 allowed localized ROS generation to mediate sustained Src oxidation and activation. |
| 653 | 23612968 | To determine the mechanism of Nox4 recruitment, we analyzed the role of Grb2, a component of the SHPS-1 signaling complex. |
| 654 | 23612968 | We determined that Nox4 Tyr-491 was phosphorylated after IGF-I stimulation and was responsible for Nox4 binding to the SH2 domain of Grb2. |
| 655 | 23612968 | Overexpression of a Nox4 mutant, Y491F, prevented Nox4/Grb2 association. |
| 656 | 23612968 | Importantly, it also prevented Nox4 recruitment to SHPS-1. |
| 657 | 23612968 | The role of Grb2 was confirmed using a Pyk2 Y881F mutant, which blocked Grb2 recruitment to SHPS-1. |
| 658 | 23612968 | Cells expressing this mutant had impaired Nox4 recruitment to SHPS-1. |
| 659 | 23612968 | IGF-I-stimulated downstream signaling and biological actions were also significantly impaired in Nox4 Y491F-overexpressing cells. |
| 660 | 23612968 | Disruption of Nox4 recruitment to SHPS-1 in aorta from diabetic mice inhibited IGF-I-stimulated Src oxidation and activation as well as cell proliferation. |
| 661 | 23612968 | Recruitment of Nox4 to a plasma membrane scaffold is required for localized reactive oxygen species generation and sustained Src activation in response to insulin-like growth factor-I. |
| 662 | 23612968 | Nox4-derived ROS is increased in response to hyperglycemia and is required for IGF-I-stimulated Src activation. |
| 663 | 23612968 | This study was undertaken to determine the mechanism by which Nox4 mediates sustained Src activation. |
| 664 | 23612968 | IGF-I stimulated sustained Src activation, which occurred primarily on the SHPS-1 scaffold protein. |
| 665 | 23612968 | In vitro oxidation experiments indicated that Nox4-derived ROS was able to oxidize Src when they are in close proximity, and Src oxidation leads to its activation. |
| 666 | 23612968 | Therefore we hypothesized that Nox4 recruitment to the plasma membrane scaffold SHPS-1 allowed localized ROS generation to mediate sustained Src oxidation and activation. |
| 667 | 23612968 | To determine the mechanism of Nox4 recruitment, we analyzed the role of Grb2, a component of the SHPS-1 signaling complex. |
| 668 | 23612968 | We determined that Nox4 Tyr-491 was phosphorylated after IGF-I stimulation and was responsible for Nox4 binding to the SH2 domain of Grb2. |
| 669 | 23612968 | Overexpression of a Nox4 mutant, Y491F, prevented Nox4/Grb2 association. |
| 670 | 23612968 | Importantly, it also prevented Nox4 recruitment to SHPS-1. |
| 671 | 23612968 | The role of Grb2 was confirmed using a Pyk2 Y881F mutant, which blocked Grb2 recruitment to SHPS-1. |
| 672 | 23612968 | Cells expressing this mutant had impaired Nox4 recruitment to SHPS-1. |
| 673 | 23612968 | IGF-I-stimulated downstream signaling and biological actions were also significantly impaired in Nox4 Y491F-overexpressing cells. |
| 674 | 23612968 | Disruption of Nox4 recruitment to SHPS-1 in aorta from diabetic mice inhibited IGF-I-stimulated Src oxidation and activation as well as cell proliferation. |
| 675 | 23612968 | Recruitment of Nox4 to a plasma membrane scaffold is required for localized reactive oxygen species generation and sustained Src activation in response to insulin-like growth factor-I. |
| 676 | 23612968 | Nox4-derived ROS is increased in response to hyperglycemia and is required for IGF-I-stimulated Src activation. |
| 677 | 23612968 | This study was undertaken to determine the mechanism by which Nox4 mediates sustained Src activation. |
| 678 | 23612968 | IGF-I stimulated sustained Src activation, which occurred primarily on the SHPS-1 scaffold protein. |
| 679 | 23612968 | In vitro oxidation experiments indicated that Nox4-derived ROS was able to oxidize Src when they are in close proximity, and Src oxidation leads to its activation. |
| 680 | 23612968 | Therefore we hypothesized that Nox4 recruitment to the plasma membrane scaffold SHPS-1 allowed localized ROS generation to mediate sustained Src oxidation and activation. |
| 681 | 23612968 | To determine the mechanism of Nox4 recruitment, we analyzed the role of Grb2, a component of the SHPS-1 signaling complex. |
| 682 | 23612968 | We determined that Nox4 Tyr-491 was phosphorylated after IGF-I stimulation and was responsible for Nox4 binding to the SH2 domain of Grb2. |
| 683 | 23612968 | Overexpression of a Nox4 mutant, Y491F, prevented Nox4/Grb2 association. |
| 684 | 23612968 | Importantly, it also prevented Nox4 recruitment to SHPS-1. |
| 685 | 23612968 | The role of Grb2 was confirmed using a Pyk2 Y881F mutant, which blocked Grb2 recruitment to SHPS-1. |
| 686 | 23612968 | Cells expressing this mutant had impaired Nox4 recruitment to SHPS-1. |
| 687 | 23612968 | IGF-I-stimulated downstream signaling and biological actions were also significantly impaired in Nox4 Y491F-overexpressing cells. |
| 688 | 23612968 | Disruption of Nox4 recruitment to SHPS-1 in aorta from diabetic mice inhibited IGF-I-stimulated Src oxidation and activation as well as cell proliferation. |
| 689 | 23859619 | Although AMPK activation inhibits tumor growth by targeting multiple signaling pathways relevant to tumorigenesis, under certain cellular contexts or certain stages of tumor development, AMPK might act as a protective response to metabolic stresses, such as nutrient deprivation, low oxygen, and low pH, or as downstream effectors of oncogenic proteins, including androgen receptor, hypoxia-inducible factor-1α, c-Src, and MYC. |
| 690 | 23942551 | Inhibition of Src kinase blocks high glucose-induced EGFR transactivation and collagen synthesis in mesangial cells and prevents diabetic nephropathy in mice. |
| 691 | 23942551 | High glucose stimulated Src, TACE, epidermal growth factor receptor (EGFR), mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK1/2, p38), and collagen IV accumulation in mesangial cells. |
| 692 | 23942551 | PP2 and SU6656 blocked high glucose-stimulated phosphorylation of Src Tyr-416, EGFR, and MAPKs. |
| 693 | 23942551 | These inhibitors and Src knockdown by siRNA, as well as TAPI-2, also abrogated high glucose-induced phosphorylation of these targets and collagen IV accumulation. |
| 694 | 23942551 | In STZ-diabetic mice, albuminuria, increased Src pTyr-416, TACE activation, ERK and EGFR phosphorylation, glomerular collagen accumulation, and podocyte loss were inhibited by PP2. |
| 695 | 23942551 | These data indicate a role for Src in a high glucose-Src-TACE-heparin-binding epidermal growth factor-EGFR-MAPK-signaling pathway to collagen accumulation. |
| 696 | 23942551 | Inhibition of Src kinase blocks high glucose-induced EGFR transactivation and collagen synthesis in mesangial cells and prevents diabetic nephropathy in mice. |
| 697 | 23942551 | High glucose stimulated Src, TACE, epidermal growth factor receptor (EGFR), mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK1/2, p38), and collagen IV accumulation in mesangial cells. |
| 698 | 23942551 | PP2 and SU6656 blocked high glucose-stimulated phosphorylation of Src Tyr-416, EGFR, and MAPKs. |
| 699 | 23942551 | These inhibitors and Src knockdown by siRNA, as well as TAPI-2, also abrogated high glucose-induced phosphorylation of these targets and collagen IV accumulation. |
| 700 | 23942551 | In STZ-diabetic mice, albuminuria, increased Src pTyr-416, TACE activation, ERK and EGFR phosphorylation, glomerular collagen accumulation, and podocyte loss were inhibited by PP2. |
| 701 | 23942551 | These data indicate a role for Src in a high glucose-Src-TACE-heparin-binding epidermal growth factor-EGFR-MAPK-signaling pathway to collagen accumulation. |
| 702 | 24002704 | Effects of sevoflurane pretreatment on renal Src and FAK expression in diabetic rats after renal ischemia/reperfusion injury. |
| 703 | 24002704 | The aim of this study was to determine if sevoflurane pretreatment could help preserve renal function in rats with diabetes mellitus (DM) by altering non-receptor tyrosine kinases steroid receptor coactivator (Src) and focal adhesion kinase (FAK) expression (Src and FAK are mediators of cellular apoptosis and necrosis). |
| 704 | 24002704 | After 24 h, serum creatinine (Cr) and blood urea nitrogen (BUN) levels, and renal Src and FAK expression (immunohistochemistry) were assessed. |
| 705 | 24002704 | Compared with rats in C, rats in D had significantly higher Cr and BUN levels, but significantly lower renal Src and FAK expression. |
| 706 | 24002704 | Rats in E had significantly lower serum Cr and BUN levels and significantly higher renal Src and FAK expression levels than rats in D. |
| 707 | 24002704 | Our findings suggest that sevoflurane pretreatment in rats with DM protects the kidneys from ischemia/reperfusion injury in part due to increased renal Src and FAK expression. |
| 708 | 24002704 | Effects of sevoflurane pretreatment on renal Src and FAK expression in diabetic rats after renal ischemia/reperfusion injury. |
| 709 | 24002704 | The aim of this study was to determine if sevoflurane pretreatment could help preserve renal function in rats with diabetes mellitus (DM) by altering non-receptor tyrosine kinases steroid receptor coactivator (Src) and focal adhesion kinase (FAK) expression (Src and FAK are mediators of cellular apoptosis and necrosis). |
| 710 | 24002704 | After 24 h, serum creatinine (Cr) and blood urea nitrogen (BUN) levels, and renal Src and FAK expression (immunohistochemistry) were assessed. |
| 711 | 24002704 | Compared with rats in C, rats in D had significantly higher Cr and BUN levels, but significantly lower renal Src and FAK expression. |
| 712 | 24002704 | Rats in E had significantly lower serum Cr and BUN levels and significantly higher renal Src and FAK expression levels than rats in D. |
| 713 | 24002704 | Our findings suggest that sevoflurane pretreatment in rats with DM protects the kidneys from ischemia/reperfusion injury in part due to increased renal Src and FAK expression. |
| 714 | 24002704 | Effects of sevoflurane pretreatment on renal Src and FAK expression in diabetic rats after renal ischemia/reperfusion injury. |
| 715 | 24002704 | The aim of this study was to determine if sevoflurane pretreatment could help preserve renal function in rats with diabetes mellitus (DM) by altering non-receptor tyrosine kinases steroid receptor coactivator (Src) and focal adhesion kinase (FAK) expression (Src and FAK are mediators of cellular apoptosis and necrosis). |
| 716 | 24002704 | After 24 h, serum creatinine (Cr) and blood urea nitrogen (BUN) levels, and renal Src and FAK expression (immunohistochemistry) were assessed. |
| 717 | 24002704 | Compared with rats in C, rats in D had significantly higher Cr and BUN levels, but significantly lower renal Src and FAK expression. |
| 718 | 24002704 | Rats in E had significantly lower serum Cr and BUN levels and significantly higher renal Src and FAK expression levels than rats in D. |
| 719 | 24002704 | Our findings suggest that sevoflurane pretreatment in rats with DM protects the kidneys from ischemia/reperfusion injury in part due to increased renal Src and FAK expression. |
| 720 | 24002704 | Effects of sevoflurane pretreatment on renal Src and FAK expression in diabetic rats after renal ischemia/reperfusion injury. |
| 721 | 24002704 | The aim of this study was to determine if sevoflurane pretreatment could help preserve renal function in rats with diabetes mellitus (DM) by altering non-receptor tyrosine kinases steroid receptor coactivator (Src) and focal adhesion kinase (FAK) expression (Src and FAK are mediators of cellular apoptosis and necrosis). |
| 722 | 24002704 | After 24 h, serum creatinine (Cr) and blood urea nitrogen (BUN) levels, and renal Src and FAK expression (immunohistochemistry) were assessed. |
| 723 | 24002704 | Compared with rats in C, rats in D had significantly higher Cr and BUN levels, but significantly lower renal Src and FAK expression. |
| 724 | 24002704 | Rats in E had significantly lower serum Cr and BUN levels and significantly higher renal Src and FAK expression levels than rats in D. |
| 725 | 24002704 | Our findings suggest that sevoflurane pretreatment in rats with DM protects the kidneys from ischemia/reperfusion injury in part due to increased renal Src and FAK expression. |
| 726 | 24002704 | Effects of sevoflurane pretreatment on renal Src and FAK expression in diabetic rats after renal ischemia/reperfusion injury. |
| 727 | 24002704 | The aim of this study was to determine if sevoflurane pretreatment could help preserve renal function in rats with diabetes mellitus (DM) by altering non-receptor tyrosine kinases steroid receptor coactivator (Src) and focal adhesion kinase (FAK) expression (Src and FAK are mediators of cellular apoptosis and necrosis). |
| 728 | 24002704 | After 24 h, serum creatinine (Cr) and blood urea nitrogen (BUN) levels, and renal Src and FAK expression (immunohistochemistry) were assessed. |
| 729 | 24002704 | Compared with rats in C, rats in D had significantly higher Cr and BUN levels, but significantly lower renal Src and FAK expression. |
| 730 | 24002704 | Rats in E had significantly lower serum Cr and BUN levels and significantly higher renal Src and FAK expression levels than rats in D. |
| 731 | 24002704 | Our findings suggest that sevoflurane pretreatment in rats with DM protects the kidneys from ischemia/reperfusion injury in part due to increased renal Src and FAK expression. |
| 732 | 24002704 | Effects of sevoflurane pretreatment on renal Src and FAK expression in diabetic rats after renal ischemia/reperfusion injury. |
| 733 | 24002704 | The aim of this study was to determine if sevoflurane pretreatment could help preserve renal function in rats with diabetes mellitus (DM) by altering non-receptor tyrosine kinases steroid receptor coactivator (Src) and focal adhesion kinase (FAK) expression (Src and FAK are mediators of cellular apoptosis and necrosis). |
| 734 | 24002704 | After 24 h, serum creatinine (Cr) and blood urea nitrogen (BUN) levels, and renal Src and FAK expression (immunohistochemistry) were assessed. |
| 735 | 24002704 | Compared with rats in C, rats in D had significantly higher Cr and BUN levels, but significantly lower renal Src and FAK expression. |
| 736 | 24002704 | Rats in E had significantly lower serum Cr and BUN levels and significantly higher renal Src and FAK expression levels than rats in D. |
| 737 | 24002704 | Our findings suggest that sevoflurane pretreatment in rats with DM protects the kidneys from ischemia/reperfusion injury in part due to increased renal Src and FAK expression. |