ライフサイエンスコーパス: IRS-1

1 IRS-1 also sequestered SHP-2.

2 IRS-1 and Akt phosphorylation were decreased, whereas ME

3 IRS-1 couples insulin and other trophic factor receptors

4 IRS-1 lacking the SAIN domain does not interact with Rap

5 nregulation of insulin receptor substrate 1 (IRS-1) and dominant-negative IGF-1R sensitized ACL cells

6 Insulin receptor substrate 1 (IRS-1) and IRS-2 are cytoplasmic adaptor proteins that m

7 howed that the insulin receptor substrate 1 (IRS-1) expression and insulin-induced Akt phosphorylatio

8 expression of insulin receptor substrate 1 (IRS-1) phosphorylated at serine residue 312 was more app

9 reased AKT and insulin receptor substrate 1 (IRS-1) phosphorylation, system A activity, and SNAT2 exp

10 Insulin receptor substrate 1 (IRS-1) plays a key role in insulin signaling, thus enabl

11 Smad2 S465/67, insulin receptor substrate 1 (IRS-1) S612, mitogen-activated ERK kinase 1/2 (MEK1/2) S

12 on the IGF-IR- insulin receptor substrate 1 (IRS-1) signaling complex, a molecular scenario that para

13 tion levels of insulin receptor substrate 1 (IRS-1) Tyr(896) and Akt Ser(473) in response to insulin.

14 ocking protein insulin receptor substrate 1 (IRS-1) was down-regulated after prolonged insulin but no

15 we identified insulin receptor substrate 1 (IRS-1), a critical mediator of the insulin/insulin-like

16 phorylation of insulin receptor substrate 1 (IRS-1), along with inhibition of insulin signaling steps

17 o-immunoprecipitation of IR, IR substrate 1 (IRS-1), and IGF-1R, and increased IRS-1 and Akt phosphor

18 to the adaptor insulin receptor substrate 1 (IRS-1), and IRS-1 knockdown enhances the antitumor effec

19 led to loss of insulin receptor substrate 1 (IRS-1), thereby impairing insulin/IGF-1 signaling and en

20 ect of BMP7 in insulin receptor substrate 1 (IRS-1)-deficient brown preadipocytes, which exhibit a se

21 affold protein insulin receptor substrate 1 (IRS-1).

22 phorylation of insulin receptor substrate-1 (IRS-1) and -2, and Akt was significantly attenuated in l

23 tein levels of insulin receptor substrate-1 (IRS-1) and impaired insulin-induced Ser308 phosphorylati

24 nase (JNK) and insulin receptor substrate-1 (IRS-1) at Ser-307 were increased (P<0.05) in OB fetal he

25 hosphorylating insulin receptor substrate-1 (IRS-1) at Ser-636/639.

26 se B (AKT) and insulin receptor substrate-1 (IRS-1) in the hypothalamic arcuate was determined.

27 The insulin receptor substrate-1 (IRS-1) is a docking protein of the insulin-like growth f

28 Insulin receptor substrate-1 (IRS-1) is a signaling adaptor protein that interfaces wi

29 phorylation of insulin receptor substrate-1 (IRS-1) on Tyr(989), a canonical binding site for the 85-

30 Insulin receptor substrate-1 (IRS-1) plays a central role in transducing the insulin s

31 d-36 decreased insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation and IRS-1-and IRS-2-asso

32 t the level of insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation, and skeletal muscle ins

33 ssociated with insulin receptor substrate-1 (IRS-1) was attenuated (P < 0.05), in agreement with the

34 The insulin receptor substrate-1 (IRS-1), a docking protein for both the type 1 insulin-li

35 mulation TrkA, insulin receptor substrate-1 (IRS-1), INSR (and presumably other proteins) forms a com

36 e receptor and insulin receptor substrate-1 (IRS-1), leading to activation of the PKB/Akt and MAPK/ER

37 ress including insulin receptor substrate-1 (IRS-1), phosphatidyl inositol-3 kinase (PI3K), Mammalian

38 naling protein insulin receptor substrate-1 (IRS-1), shown here to be a transcriptional target of Wnt

39 expression of insulin receptor substrate-1 (IRS-1), the principle intracellular substrate for phosph

40 t the level of insulin receptor substrate-1 (IRS-1).

41 re it degraded insulin receptor substrate-1 (IRS-1).

42 daptor protein insulin receptor substrate-1 (IRS-1).

43 ins, including insulin receptor substrate-1 (IRS-1).

44 ylation of the insulin receptor substrate-1 (IRS-1).

45 that relies on the IGF receptor substrate-1 (IRS-1).

46 receptor (IR)/insulin receptor substrate-1 (IRS-1)/Akt pathway in the early phase of adipogenesis.

47 e insulin (IN)/insulin receptor substrate-1 (IRS-1)/mitogen-associated protein kinase (MAPK) and the

48 ely these data support a role for the IGF-1R-IRS-1 pathway in both ALK TKI-sensitive and ALK TKI-resi

49 ion with a blocking peptide inhibited IGF-1R/IRS-1/Akt activation and also restored AI sensitivity.

50 an exosomal levels of extracted P-serine 312-IRS-1 and P-pan-tyrosine-IRS-1 by ELISA and the ratio of

51 e factor, R) for AD and DM2 and P-serine 312-IRS-1 and R for FTD were significantly different from th

52 IRS-1 by ELISA and the ratio of P-serine 312-IRS-1 to P-pan-tyrosine-IRS-1 (insulin resistance factor

53 nts with AD, exosomal levels of P-serine 312-IRS-1, P-pan-tyrosine-IRS-1, and R were significantly di

54 tions in IRS-1 phosphorylated at serine 616 (IRS-1 pS(6)(1)(6)) and IRS-1 pS(6)(3)(6)/(6)(3)(9).

55 sts of Cul7-/- mice were found to accumulate IRS-1 and exhibit increased activation of IRS-1's downst

56 of an ERalpha/IRS-1 complex, which activated IRS-1 and directed signaling via the PI3K/Akt pathway.

57 feedback mechanisms, such as those affecting IRS-1 signaling to PI3K, to regulate the response of Akt

58 ampal response to insulin, caused by altered IRS-1 and PTEN (phosphatase and tensin homologue on chro

59 Although IRS-1 and IRS-2 share significant homology, they regulat

60 This result was confirmed by expressing an IRS-1 mutant that had both impaired binding to IGF-IR an

61 ction to protect cancer cells from ROS in an IRS-1-dependent manner.

62 Expression of an IRS-1 mutant (Y1179F/Y1229F) reduced IRS-1/SHP-2 associa

63 or insulin receptor substrate 1 (IRS-1), and IRS-1 knockdown enhances the antitumor effects of ALK in

64 with this finding, the levels of IGF-1R and IRS-1 are increased in biopsy samples from patients prog

65 Levels of IRS-1 pS(6)(1)(6) and IRS-1 pS(6)(3)(6)/(6)(3)(9) and their activated kinases

66 ylated at serine 616 (IRS-1 pS(6)(1)(6)) and IRS-1 pS(6)(3)(6)/(6)(3)(9).

67 s vis a vis insulin but may protect IR-A and IRS-1 from down-regulation thereby evoking sustained and

68 horylation was decreased, p38MAPK, Akt1, and IRS-1 phosphorylation at Ser-307 were increased, togethe

69 mutated to alanine (Tg IRS-1 Ser-->Ala) and IRS-1 wild-type (Tg IRS-1 WT) transgenic mice and examin

70 lucose metabolism via inhibition of AMPK and IRS-1 underscore the important role of inflammation in t

71 p identified between neutrophil elastase and IRS-1 in LSL-K-ras mice was also identified in human lun

72 CRP with Abeta plaques, tau-like fibrils and IRS-1/P-Tau positive neurons and high mCRP-levels spread

73 preformed complex with PI3K heterodimer and IRS-1, it is an A-kinase anchoring protein that binds th

74 cells, tyrosine phosphorylation of INSR and IRS-1 is dependent upon the functional TrkA kinase domai

75 reveal that IQGAP1 is a scaffold for IR and IRS-1 and implicate IQGAP1 as a participant in insulin s

76 show that IQGAP1 associates with both IR and IRS-1 and influences insulin action.

77 sistent with these observations, both IR and IRS-1 co-immunoprecipitated with IQGAP1 from cells.

78 gative feedback loop between mTOR-p70S6K and IRS-1 that mediates rapamycin-directed IGF-IR signaling.

79 nted TNF-induced Ser-270 phosphorylation and IRS-1 protein degradation.

80 trate-1 (IRS-1) tyrosine phosphorylation and IRS-1-and IRS-2-associated PI 3-kinase activities.

81 Notably, rictor and IRS-1 phosphorylation by p70S6K1 attenuate insulin actio

82 ecular level, Raptor binds the SAIN (Shc and IRS-1 NPXY binding) domain of IRS-1 and regulates the ph

83 We observed similar effects on SOCS3 and IRS-1 when we treated cultured muscle myotubes with rhIL

84 abolished insulin-stimulated AKT Thr308 and IRS-1 Tyr612 phosphorylation, system A activity, and SNA

85 ated transgenic mice in which the HBx (ATX), IRS-1, or both (ATX+/IRS-1) genes were expressed under a

86 in which the HBx (ATX), IRS-1, or both (ATX+/IRS-1) genes were expressed under a liver-specific promo

87 (ATX or IRS-1) did not develop tumors, ATX+/IRS-1+ double transgenic livers had increased frequency

88 chondrocytes, which possessed elevated basal IRS-1 (Ser-312) and ERK phosphorylation, IGF-I failed to

89 Hyperglycemia also reduces the basal IRS-1 concentration and IGF-I-stimulated IRS-1-linked si

90 Because IRS-1 is down-regulated in states of insulin resistance

91 The association between IRS-1 genetic variants, platelet function, and the risk

92 n signaling via decreased activation of both IRS-1 and Akt.

93 itide 3-kinase (PI3K) interactions with both IRS-1 and IRS-2.

94 placental S6K, S6 ribosomal protein, 4E-BP1, IRS-1, Akt, ERK-1/2, and GSK-3.

95 ization, indicating sequestration of aPKC by IRS-1 away from MARK2.

96 pancy of the rDNA and cyclin D1 promoters by IRS-1 and the activation of the cyclin D1, c-myc, and rD

97 The ability of PKA to commandeer IRS-1 and GAB2, adaptors that normally integrate recepto

98 dose of glucocorticoids exhibited decreased IRS-1-associated PI3K activity in muscle and progressive

99 Defective IRS-1 degradation was due to attenuated expression and p

100 showed that, as neutrophil elastase degraded IRS-1, there was increased interaction between phosphati

101 ly, plasma levels of exosomal neural-derived IRS-1 phosphorylated at serine residue 307 (correspondin

102 In diabetes, IRS-1 is down-regulated, and cells become resistant to i

103 ession for insulin signaling proteins, i.e., IRS-1 and IRS-2, were not increased with CR, although a

104 ression of selected PR target genes (HB-EGF, IRS-1, and STC1) was significantly elevated in cells con

105 ling was mediated by formation of an ERalpha/IRS-1 complex, which activated IRS-1 and directed signal

106 failed to stimulate formation of the ERalpha/IRS-1 complex, allowing signaling to proceed via the alt

107 d AMPKalpha, patient leukocytes also express IRS-1 phosphorylated on Ser(312), Akt phosphorylated on

108 ors is twice as large when the cells express IRS-1.

109 ative feedback input to the signaling factor IRS-1.

110 epatocytes, suggesting a novel mechanism for IRS-1 inhibition.

111 phrin-PI3K binding site and renders PI3K for IRS-1, thereby activating mTORC1.

112 ranslocation and negated the requirement for IRS-1.

113 Further, IRS-1 interacts with p62 through its YMXM motifs at Tyr-

114 d responses to insulin signaling in the IR-->IRS-1-->PI3K signaling pathway with greatly reduced resp

115 he intracellular domain of IR display higher IRS-1 phosphorylation, stronger regulation of genes in m

116 270, Ser-307, Ser-636, and Ser-1101 in human IRS-1 (Ser-265, Ser-302, Ser-632, and Ser-1097, in roden

117 This study identifies IRS-1 as a key regulator of PI3K within malignant cells.

118 Impaired IRS-1 signaling was also present in the hippocampi of Tg

119 inhibitor preadipocyte factor 1 (Pref-1) in IRS-1-null cells was markedly reduced by 3 days of BMP7

120 reater in SMLPL(-/-) mice without changes in IRS-1 tyrosine phosphorylation and phosphatidylinositol

121 ly greater increase in SOCS3 and decrease in IRS-1 compared with either rhIL-6 or SAA1 alone.

122 istently associated with basal elevations in IRS-1 phosphorylated at serine 616 (IRS-1 pS(6)(1)(6)) a

123 n at the Y(608)XXM PI3K p85 binding motif in IRS-1 and possibly at PDK1 as well.

124 suggest that whilst programmed reductions in IRS-1 are associated with increased levels of miR-126 an

125 VSMC dedifferentiation, was up-regulated in IRS-1(-/-) mice, and the differentiation inducer myocard

126 in tyrosine phosphorylation of Y(608)XXM in IRS-1, one of the two main PI3K p85 binding motifs.

127 , dual expression that activates both the IN/IRS-1/MAPK and Wnt/beta-catenin cascades is sufficient t

128 edly triggers IRS-1 downregulation, inactive IRS-1 accumulated in mTORC2-disrupted cells.

129 Key insulin signaling proteins, including IRS-1, IRS-2, and PDK1, are substrates for OGT, suggesti

130 activity of PI3K/AKT, but it also increased IRS-1 activity.

131 bstrate 1 (IRS-1), and IGF-1R, and increased IRS-1 and Akt phosphorylation accompany receptor activat

132 independent mechanisms, including increased IRS-1 protein degradation.

133 e, nicotine exposure significantly increased IRS-1(ser636) phosphorylation and decreased insulin sens

134 role for S6K1 in mediating TNF-alpha-induced IRS-1 inhibition that led to impaired insulin-stimulated

135 phosphorylation and inhibited IGF-I-induced IRS-1 (Tyr-612) and Akt phosphorylation.

136 activated the JNK/TNF-alpha pathway, induced IRS-1 phosphorylation at multiple serine residues, and i

137 m the previously described rapamycin-induced IRS-1 stabilization mechanism.

138 of VSMC cultures to a peptide that inhibited IRS-1/IGF-IR interaction showed that IRS-1 binding to IG

139 ctivates the mTOR/S6K1 pathway in inhibiting IRS-1 function and perturbs glucose metabolism via downr

140 pSTAT3 via the IL-6 receptor, which inhibits IRS 1/2 phosphorylation.

141 h marked changes in insulin receptor (InsR), IRS-1, IRS-2, Akt activation, and a macrophage and adipo

142 uppressed AGER1 and SIRT1, and altered InsR, IRS-1, IRS-2 phosphorylation, and nuclear factor kappa-l

143 eptin resistance by an improvement of the IR/IRS-1/Akt and JAK2/STAT3 pathways in the hypothalamus.

144 n showed more significant inhibition of JNK, IRS-1, and tau phosphorylation.

145 oth for 4 months reduced phosphorylated JNK, IRS-1, and tau and prevented the degradation of total IR

146 terations in cardiac PI3K-Akt, AMPK, and JNK-IRS-1 signaling pathways that would predispose them to i

147 PIP(3) and the enzymes regulating its level, IRS-1-associated phosphatidylinositol 3-kinase (PI3K) an

148 Mechanistically, IRS-1 deficiency promotes Janus kinase/signal transducer

149 ion of Fbw8 to the cytosol where it mediates IRS-1 degradation.

150 tudy, we show that IRS-2 expression, but not IRS-1 expression, is positively regulated by hypoxia, wh

151 Based on data implicating IRS-2 but not IRS-1 in breast cancer invasion, survival, and metastasi

152 insulin receptor substrate (IRS)-2, but not IRS-1, is involved in regulation of IGF-IR expression, w

153 e cytoskeleton contributes to IRS-2- but not IRS-1-mediated activation of AKT by IGF-1.

154 eonine phosphorylation alters the ability of IRS-1 to transduce the insulin signal.

155 ited decreased phosphorylation/activation of IRS-1 and AKT following stimulation by insulin, insulin-

156 trate (IRS)-1 in the liver and activation of IRS-1 and protein kinase C by insulin in liver and muscl

157 te IRS-1 and exhibit increased activation of IRS-1's downstream Akt and MEK/ERK pathways, these null

158 IGFIR signaling disrupted the association of IRS-1 with PI3K and restored the ability of gefitinib to

159 ptor (IGFIR) and constitutive association of IRS-1 with PI3K.

160 ulin receptor, IRS-1, and the association of IRS-1 with PI3K.

161 ant of IRS-1 (S270A) impaired association of IRS-1 with S6K1 resulting in diminished phosphorylation

162 A functional consequence of IRS-1 inhibition was reflected in a decrease in GLUT4 pr

163 metastasis, we assessed the contribution of IRS-1 and IRS-2 to aerobic glycolysis, which is known to

164 ling-1, implicating increased degradation of IRS-1 as an underlying mechanism.

165 stance due to mTORC2-mediated degradation of IRS-1.

166 Here we show that deletion of IRS-1 expression in VSMCs in non-diabetic mice results i

167 tion inhibited tyrosine dephosphorylation of IRS-1 or IRS-2 and increased the ability of IRS proteins

168 SAIN (Shc and IRS-1 NPXY binding) domain of IRS-1 and regulates the phosphorylation of IRS-1 at Ser-

169 larly, the phosphotyrosine-binding domain of IRS-1 mediates a direct interaction with the C-terminal

170 egulation of the relative gene expression of IRS-1, PI3K and Akt in the insulin signaling pathway, wh

171 These findings illuminate a new function of IRS-1: that of maintaining cells in their normal, differ

172 JNK mediates Abeta oligomer inactivation of IRS-1 and phospho-tau pathology and that dietary treatme

173 Inhibition of IRS-1 expression was observed in HCV-infected hepatocyte

174 insulin resistance, including inhibition of IRS-1 mRNA levels and activation of gluconeogenesis-rela

175 r a small molecule inhibitor or knockdown of IRS-1 expression using shRNA diminished heparanase-media

176 Knockdown of IRS-1 using small interfering RNA or adenovirus-mediated

177 ts PI 3-kinase/Akt signaling at the level of IRS-1 and suggest that mTOR signaling toward Akt is scaf

178 sulin responses were maximal at the level of IRS-1 and were consistently associated with basal elevat

179 The increased level of IRS-1 drives activation of mitochondrial biogenesis; fur

180 ct feedback loops converging at the level of IRS-1.

181 Levels of IRS-1 pS(6)(1)(6) and IRS-1 pS(6)(3)(6)/(6)(3)(9) and th

182 A point mutant of IRS-1 (S270A) impaired association of IRS-1 with S6K1 re

183 ing cessation occurred with normalization of IRS-1(ser636) phosphorylation.

184 for activity, we show that overexpression of IRS-1 reduces the phosphorylation of MARK2 and enhances

185 reement with the increased phophorylation of IRS-1 at serine 1011.

186 Here, we show that serine phosphorylation of IRS-1 (IRS-1pSer) is common to both diseases.

187 increased active JNK and phosphorylation of IRS-1 (Ser616) and tau (Ser422) in cultured hippocampal

188 ed a strong and sustained phosphorylation of IRS-1 (Tyr-612) and Akt (Ser-473) and transient ERK phos

189 rly inhibited JNK and the phosphorylation of IRS-1 and tau in cultured hippocampal neurons.

190 resses insulin-stimulated phosphorylation of IRS-1 at Ser-636/639 and stabilizes IRS-1 after long ter

191 f IRS-1 and regulates the phosphorylation of IRS-1 at Ser-636/639 by mTOR.

192 Concurrently, serine phosphorylation of IRS-1 at serine 632/635, which is phosphorylated by ROCK

193 1 resulting in diminished phosphorylation of IRS-1 at three other S6K1 phosphorylation sites (Ser-307

194 This led to phosphorylation of IRS-1 by S6K1 at multiple serine residues including Ser-

195 Tyrosine phosphorylation of IRS-1 initiates insulin signaling, whereas serine/threon

196 sphorylation and tyrosine phosphorylation of IRS-1 itself.

197 and increased inhibitory phosphorylation of IRS-1 on Ser 1101.

198 ably through the negative phosphorylation of IRS-1 on Ser-1101.

199 a demonstrate that serine phosphorylation of IRS-1 plays an important role in mediating fat-induced i

200 As a result, the phosphorylation of IRS-1 serine 307 induced by anisomycin was abolished, le

201 insulin receptor-mediated phosphorylation of IRS-1 was examined.

202 protein-mediated Ser(312) phosphorylation of IRS-1 was inhibited by JNK (SP600125) and phosphatidylin

203 et)CCL5, abolished the de-phosphorylation of IRS-1(S302) and insulin signal activation.

204 -alpha and decreasing the phosphorylation of IRS-1(Ser307) while increasing tyrosine phosphorylation

205 A significantly decreased phosphorylation of IRS-1(Ser307), which was further decreased after salmete

206 owed that insulin-induced phosphorylation of IRS-1, Akt, and eNOS was significantly decreased in ZF r

207 ne and decreased tyrosine phosphorylation of IRS-1, and decreased insulin signaling.

208 g steps, such as tyrosine phosphorylation of IRS-1, and phosphorylation of Akt and ERK.

209 via the inhibitory serine phosphorylation of IRS-1, notably on serine 1101 (Ser-1101).

210 rylation but not tyrosine phosphorylation of IRS-1.

211 l as a decrease in serine phosphorylation of IRS-1.

212 tions of decorin promoted down-regulation of IRS-1, one of the critical proteins of the IGF-IR pathwa

213 ere, we describe a new negative regulator of IRS-1, the p90 ribosomal S6 kinase (RSK).

214 osphorylation of Akt, a downstream target of IRS-1.

215 ion of the PI3K p85 binding motifs (YXXM) of IRS-1 and results in a concomitant reduction in tyrosine

216 effects of a post-weaning obesogenic diet on IRS-1 are mediated by miR-126 independent mechanisms, in

217 re not as marked in male offspring with only IRS-1, VEGF-A, Glut 4 and LPL being up-regulated in thos

218 gest that continued expression of the ATX or IRS-1 transgenes can contribute to hepatocyte transforma

219 Whereas mice with a single transgene (ATX or IRS-1) did not develop tumors, ATX+/IRS-1+ double transg

220 (VSMC) responses to IGF-I, we overexpressed IRS-1 in VSMCs maintained in high glucose.

221 by reducing the expression of total IRS-1, p-IRS-1 (tyr632), and p-AKT (ser473); it also activates th

222 n in endothelial cells and neurons through p-IRS-1, p-Tau and p-ERK1/2-which was blocked following pr

223 Increased phospho-IRS-1 is found in AD brain and insulin-resistant tissues

224 4 membrane translocation and reduced phospho-IRS-1(S302) through AMPKalpha-S6 Kinase.

225 fat increased active JNK and phosphorylated IRS-1 and tau.

226 Moreover, recombinant RSK phosphorylated IRS-1 C-terminal fragment on Ser-1101, which was prevent

227 S6K directly phosphorylates IRS-1 on multiple serine residues to inhibit insulin sig

228 ) showed that RSK selectively phosphorylates IRS-1 on Ser-1101.

229 n-stimulated IRS-1 tyrosine phosphorylation, IRS-1 docking with phosphatidylinositol 3-kinase, and Ak

230 /42 MAPK, during nicotine exposure prevented IRS-1(ser636) phosphorylation and normalized insulin sen

231 the absence of AA, insulin can still promote IRS-1 Ser-1101 phosphorylation by other kinases that rem

232 d in an in vitro kinase assay using purified IRS-1 and S6K1.

233 syl phosphorylation of the insulin receptor, IRS-1, and the association of IRS-1 with PI3K.

234 However, the expression of insulin receptor, IRS-1, IRS-2, Akt, glycogen synthase kinase-3beta, forkh

235 It directly binds to insulin receptors, IRS-1 and IRS-2, and enhances insulin sensitivity by pro

236 Proteasome inhibitor MG 132 recovered IRS-1 and TSC1/2 expression, suggesting that degradation

237 t reduce Akt phosphorylation despite reduced IRS-1 signaling.

238 f IKKepsilon activity, but not TBK1, reduced IRS-1(Ser307) phosphorylation and insulin and leptin res

239 was a prominent mechanism underlying reduced IRS-1-associated PI3K activity.

240 Surprisingly, tumors with reduced IRS-1 staining in a human lung adenocarcinoma tissue mic

241 n of an IRS-1 mutant (Y1179F/Y1229F) reduced IRS-1/SHP-2 association, and exposure of cells expressin

242 To determine if failure to down-regulate IRS-1 alters vascular smooth muscle cell (VSMC) response

243 of Sirt1 to directly deacetylate and repress IRS-1 function.

244 5, Ser-302, Ser-632, and Ser-1097, in rodent IRS-1).

245 and aPKC with the insulin-regulated scaffold IRS-1.

246 n of insulin response substrate-1 at Ser302 (IRS-1(S302)) but not IRS-2, by insulin was markedly incr

247 keletal muscle, we generated muscle-specific IRS-1 Ser(302), Ser(307), and Ser(612) mutated to alanin

248 ation of IRS-1 at Ser-636/639 and stabilizes IRS-1 after long term insulin stimulation.

249 K phosphorylation, IGF-I failed to stimulate IRS-1 (Tyr-612) or Akt phosphorylation.

250 The two pathways known to stimulate IRS-1(ser636) phosphorylation (p44/42 mitogen-activated

251 nt reversed inflammatory cytokine-stimulated IRS-1 serine phosphorylation, increased insulin signalin

252 sal IRS-1 concentration and IGF-I-stimulated IRS-1-linked signaling.

253 lation, and inhibition of insulin-stimulated IRS-1 tyrosine phosphorylation and AKT2 phosphorylation.

254 ignaling with recovery of insulin-stimulated IRS-1 tyrosine phosphorylation, IRS-1 docking with phosp

255 a significant increase in insulin-stimulated IRS-1-associated phosphatidylinositol 3-kinase activity

256 al human chondrocytes, tBHP triggered strong IRS-1 (Ser-312 and Ser-616) and ERK phosphorylation and

257 it of the insulin receptor and its substrate IRS-1 and increased insulin-induced phosphorylation of P

258 P)-serine-type 1 insulin receptor substrate (IRS-1) and less P-tyrosine-IRS-1.

259 mTORC1/S6K, the insulin receptor substrate (IRS-1) is targeted for ubiquitination and proteasomal de

260 O mice), acute diabetes minimally suppressed IRS-1-associated PI3K activity in muscle and did not cau

261 Surprisingly, IRS-1 phosphorylation was not diminished in Y325F L-cell

262 rate a key role for the CUL7 E3 in targeting IRS-1 for degradation, a process that may contribute to

263 at the E3 ubiquitin-ligase CUL7/Fbw8 targets IRS-1 for degradation, thereby implicating this enzyme i

264 Tg IRS-1 Ser-->Ala mice were protected from fat-induced ins

265 er(307), and Ser(612) mutated to alanine (Tg IRS-1 Ser-->Ala) and IRS-1 wild-type (Tg IRS-1 WT) trans

266 In contrast, Tg IRS-1 WT mice exhibited no improvement in glucose tolera

267 Furthermore, Tg IRS-1 Ser-->Ala mice displayed a significant increase in

268 (Tg IRS-1 Ser-->Ala) and IRS-1 wild-type (Tg IRS-1 WT) transgenic mice and examined insulin signaling

269 te for type I IGF receptor (IGF-IR) and that IRS-1 competitively inhibited SHPS-1 phosphorylation.

270 It has been assumed that IRS-1 promotes tumor growth through its ability to activ

271 We conclude that IRS-1 is an important factor for maintaining VSMCs in th

272 hibited IRS-1/IGF-IR interaction showed that IRS-1 binding to IGF-IR impairs SHPS-1 phosphorylation i

273 iates a reciprocal communication between the IRS-1/PI3K/Akt and IRS-2/MEK/ERK pathways that coordinat

274 es SIRT1 promoter activity and that both the IRS-1 and FKHD-L enable FoxO1-dependent SIRT1 transcript

275 ly reduced tumor burden, most notably in the IRS-1-deficient group.

276 f the C allele of the rs956115 marker of the IRS-1 gene have a hyperreactive platelet phenotype and i

277 n of TSC-1/TSC-2 significantly recovered the IRS-1 protein expression level in HCV-infected hepatocyt

278 pitation assays show that FoxO1 binds to the IRS-1 and FKHD-L sites of the SIRT1 promoter.

279 airs hippocampal response to insulin through IRS-1 and PTEN dysregulation and suggest that, in Alzhei

280 ate the mechanism by which signaling through IRS-1 and IRS-2 results in differential outcomes, we ass

281 ide a chronic proliferative stimulus through IRS-1 in the context of hepatitis Bx (HBx) protein expre

282 Thus, mTORC2 negatively feeds back to IRS-1 via control of Fbw8 stability and localization.

283 Insulin stimulated the binding of SH2B1 to IRS-1 or IRS-2.

284 udy, we further examined the status of total IRS-1 and the downstream regulation of the Akt pathway i

285 ignaling by reducing the expression of total IRS-1, p-IRS-1 (tyr632), and p-AKT (ser473); it also act

286 d tau and prevented the degradation of total IRS-1.

287 ated serine sites, which supposedly triggers IRS-1 downregulation, inactive IRS-1 accumulated in mTOR

288 ceptor substrate (IRS-1) and less P-tyrosine-IRS-1.

289 atio of P-serine 312-IRS-1 to P-pan-tyrosine-IRS-1 (insulin resistance factor, R) for AD and DM2 and

290 racted P-serine 312-IRS-1 and P-pan-tyrosine-IRS-1 by ELISA and the ratio of P-serine 312-IRS-1 to P-

291 levels of P-serine 312-IRS-1, P-pan-tyrosine-IRS-1, and R were significantly different 1 to 10 yr bef

292 studies were undertaken to determine whether IRS-1 is functioning constitutively to maintain VSMCs in

293 IGF-1 resistance and closely associated with IRS-1 dysfunction potentially triggered by Abeta oligome

294 ylinositol 3-kinase activity associated with IRS-1 or phospho-tyrosine was also reduced approximately

295 However, Ad5E1A associates with IRS-1, increasing Akt and GSK-3beta phosphorylation and

296 eted for PI3K, reducing its association with IRS-1.

297 naling pathway through its interactions with IRS-1.

298 erminus of sequestosome 1/p62 interacts with IRS-1 upon insulin stimulation.

299 iation of phosphatidylinositol 3-kinase with IRS-1, were significantly decreased.

300 ional analyses revealed that Ser-1101 within IRS-1 falls into the consensus motif of RSK.