ライフサイエンスコーパス: IRS-2

1 r null for either Irs-1 (Irs-1-/-) or Irs-2 (Irs-2-/-).

2 is dependent upon serine phosphorylation of IRS-2.

3 nase (PI3K) interactions with both IRS-1 and IRS-2.

4 of SOCS3 had no effect on ubiquitination of IRS-2.

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

6 cules insulin-receptor substrate (IRS)-1 and IRS-2.

7 insulin-induced tyrosine phosphorylation of IRS-2.

8 of transcription of IRS-1 as well as that of IRS-2.

9 receptor substrate (IRS) proteins, IRS-1 and IRS-2.

10 rine-specific dephosphorylation of IRS-1 and IRS-2.

11 via mTOR-induced Ser/Thr phosphorylation of IRS-2.

12 ress insulin receptor substrate 1 (IRS-1) or IRS-2.

13 insulin-induced tyrosine phosphorylation of IRS-2, a vital step in insulin signaling pathway, throug

14 expression of insulin receptor substrate-2 (IRS-2; a protein involved in neurotrophic signaling) in

15 Inhibition of IRS-2 action by 30 muM SSRI was associated with a marked

16 We hypothesized that negative regulation of IRS-2 activity after IL-4 stimulation is dependent upon

17 e conditioning paradigm, whereas blockade of IRS-2 activity results in avoidance of cocaine-paired co

18 The concomitant injection of IRS-1 and IRS-2 adenoviral shRNAs resulted in systemic insulin res

19 r(P)) and serine phosphorylation (Ser(P)) of IRS-2 after IL-4 stimulation.

20 d changes in insulin receptor (InsR), IRS-1, IRS-2, Akt activation, and a macrophage and adipocyte sh

21 , the expression of insulin receptor, IRS-1, IRS-2, Akt, glycogen synthase kinase-3beta, forkhead box

22 of SOCS1 inhibited ubiquitin accumulation on IRS-2, although siRNA knockdown of SOCS3 had no effect o

23 ugh insulin receptor substrate-1 (IRS-1) and IRS-2, among other factors, activate PI3K, there is litt

24 ents, insulin receptor substrate (IRS)-1 and IRS-2, an effect that could be blocked by EGF receptor (

25 ose/IGF-1-induced Ser/Thr phosphorylation of IRS-2 and decreased IRS-2 protein levels, whereas adenov

26 serine phosphatase activity increased Ser(P)-IRS-2 and decreased Tyr(P)-IRS-2 leading to reduced M2 g

27 e essential for the association of PI3K with Irs-2 and demonstrate that combined mutation of these ty

28 ecruitment of SRC-3 to two target promoters, IRS-2 and IGF-I, requires transcription factor activator

29 e with tyrosine phosphorylation of IRS-1 and IRS-2 and impair the ability of insulin to activate glyc

30 in downstream of TORC1, enhanced both Tyr(P)-IRS-2 and increased expression of all four M2 genes.

31 bited tyrosine dephosphorylation of IRS-1 or IRS-2 and increased the ability of IRS proteins to activ

32 eatment, whereas AGN194204 increased hepatic Irs-2 and insulin stimulated phospho-Akt in liver.

33 onocytes displayed greater ubiquitination of IRS-2 and lower M2 polarization than allergic monocytes

34 onversely reduced Ser/Thr phosphorylation of IRS-2 and maintained IRS-2 protein levels.

35 Intriguingly, downregulation of IRS-2 and MET contributed to the suppression of AKT sign

36 ream of TORC1, resulted in diminished Ser(P)-IRS-2 and prolonged Tyr(P)-IRS-2 as well.

37 Downstream of IRS-2 and Shc, IGF-I treatment results in strong activat

38 ulated tyrosine phosphorylation of IRS-1 and IRS-2 and subsequent p85 binding is transient and preced

39 of IRS-2, but not one with the N terminus of IRS-2 and the C terminus of IRS-1, also rescued differen

40 ed by insulin in 32D cells stably expressing IRS-2 and the insulin receptor.

41 duced increase in Ser/Thr phosphorylation of IRS-2 and the subsequent decrease in INS-1 cell IRS-2 pr

42 of insulin receptor substrate-1 (IRS-1) and IRS-2 and their association with the p85 subunit of phos

43 f the insulin receptor substrate (IRS)-1 and IRS-2 and thereby inhibited the activation of Akt, expre

44 Both silencing IRS-2 and TNFalpha treatment increase PTP and PTP-1B act

45 YP2E1 overexpression, insulin-induced IRS-1, IRS-2, and Akt phosphorylation were similarly decreased.

46 phosphorylation, increased ubiquitination of IRS-2, and enhanced M2 gene expression.

47 rectly binds to insulin receptors, IRS-1 and IRS-2, and enhances insulin sensitivity by promoting ins

48 IRS-1, IRS-2, and IRS-4 were each overexpressed in 80% of the H

49 insulin signaling proteins, including IRS-1, IRS-2, and PDK1, are substrates for OGT, suggesting pote

50 Insulin receptor substrate 1 (IRS-1) and IRS-2 are cytoplasmic adaptor proteins that mediate the

51 Insulin receptor substrate-1 (IRS-1) and IRS-2 are known to transduce and amplify signals emanati

52 ipocytes, and further suggest that IRS-1 and IRS-2 are required for the activation of Cbl/PI3K during

53 ing evidence from knockout models implicates IRS-2 as a key component of this signal transduction mec

54 We identify IRS-2 as a novel hypoxia-responsive gene and establish t

55 th microtubule-disrupting drugs, identifying IRS-2 as a potential biomarker for the response of breas

56 ancer progression, our work may also suggest IRS-2 as a useful marker for aggressive breast cancer.

57 diminished Ser(P)-IRS-2 and prolonged Tyr(P)-IRS-2 as well.

58 RS-1) tyrosine phosphorylation and IRS-1-and IRS-2-associated PI 3-kinase activities.

59 les also was low, indicating that the higher IRS-2-associated PI3-K activity did not compensate for t

60 ciated PI3-K activity was suppressed by CKD; IRS-2-associated PI3-K activity was increased.

61 betic (db/db) mice showed a 44% reduction in IRS-2-associated PI3-kinase activity stimulated by IL-4

62 In these cells, IL-4-stimulated IRS-2-associated PI3-kinase activity was reduced by 37.5

63 phosphorylation and restored IL-4-dependent IRS-2-associated PI3-kinase activity.

64 glucose alone did not impact IL-4-activated IRS-2-associated PI3-kinase.

65 d insulin receptor substrate 1- (IRS-1-) and IRS-2-associated PI3K activity in muscle and liver, resp

66 eceptor substrate 2 (IRS-2) phosphorylation, IRS-2-associated PI3K activity, and Akt activity in live

67 The Nedd4 and IRS-2 association is also required for maximal activatio

68 pitation, we found that SOCS1 complexes with IRS-2 at baseline, and this association increased after

69 esting that PKCdelta is downstream of IGF-IR/IRS-2 axis.

70 Insulin receptor substrate-2 (IRS-2) belongs to the IRS family of adaptor proteins tha

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

72 Collectively, our data indicate that Irs-2, but not Irs-1, promotes invasion by sustaining th

73 he N terminus of IRS-1 and the C terminus of IRS-2, but not one with the N terminus of IRS-2 and the

74 tact microtubule cytoskeleton contributes to IRS-2- but not IRS-1-mediated activation of AKT by IGF-1

75 The specific activation of IRS-2 by IGF-I through the IR does not result in activat

76 substrate-1 at Ser302 (IRS-1(S302)) but not IRS-2, by insulin was markedly increased in CCR5 and CCL

77 growth inhibition by IGFBP-3) with IRS-1 or IRS-2 cDNA confers sensitivity to growth inhibition by I

78 Expression of exogenous Irs-2 in Irs-2-/- cells restored the rate of glycolysis to that o

79 consumption, was diminished significantly in Irs-2-/- cells when compared with WT and Irs-1-/- cells.

80 IRS-2 colocalization with tubulin is enhanced upon Taxol

81 ur results reveal a novel mechanism by which IRS-2 contributes to the aggressive behavior of hypoxic

82 orylation of the downstream adapter protein, IRS-2, correlating with the expression of genes (ArgI, R

83 Irs-2-dependent activation of PI3K regulates the phospho

84 Taken together these results indicate that IRS-2-dependent IL-4 signaling in macrophages is impaire

85 Suppression of Glut1 expression inhibits Irs-2-dependent invasion, which links glycolysis to mamm

86 Inhibition of Gsk-3beta by Irs-2-dependent PI3K signaling promotes glucose uptake a

87 To determine the contribution of Irs-2-dependent PI3K signaling to this selective regulat

88 n target of rapamycin (mTor) activation, and Irs-2-dependent regulation of Glut1 surface expression i

89 hich Irs-1 impedes metastasis is to suppress Irs-2-dependent signaling.

90 ivity and insulin receptor substrate (IRS)-1/IRS-2 dephosphorylation was examined using in vitro kina

91 PI3K complex formation with a cell permeable IRS-2-derived tyrosine phosphopeptide inhibited IL-4-dep

92 Here, we show that IRS-1 and IRS-2, despite significant homology, play critical yet d

93 We located an I4R-like motif (IRS-2 docking sequence) in the gammaC cytoplasmic domain

94 However, Irs-2 does regulate the surface expression of glucose tr

95 nformation on the relative roles of IRS-1and IRS-2 during aPKC activation by insulin action in specif

96 ude that Nedd4-induced monoubiquitination of IRS-2 enhances IGF signalling and mitogenic activity.

97 ne manipulations and then to glucose-induced IRS-2 expression analyzed by real-time PCR and immunoblo

98 promote beta-cell survival via regulation of IRS-2 expression and a subsequent parallel protein kinas

99 teasomal degradation, resulting in decreased IRS-2 expression and increased beta-cell apoptosis.

100 patic insulin receptor substrate (IRS)-1 and IRS-2 expression and insulin-stimulated Akt-phosphorylat

101 ausing decreased ERK and CREB activation and IRS-2 expression as well as reduced cAMP levels and impa

102 e data indicate that iNOS-derived NO reduces IRS-2 expression by promoting protein degradation, at le

103 The effects of iNOS on IRS-2 expression have not yet been investigated in beta-

104 these data further the idea that controlled IRS-2 expression in beta-cells could be a therapeutic me

105 ucose metabolism was necessary for increased IRS-2 expression in beta-cells.

106 to examine if a similar mechanism controlled IRS-2 expression in beta-cells.

107 ntly prevented NO donor-induced reduction in IRS-2 expression in beta-cells.

108 In support of this mechanism, reduction of Irs-2 expression in Irs1(-/-) tumor cells restored mTor

109 eedback control of IRS signaling to decrease IRS-2 expression in liver and beta-cells is quite distin

110 rect in vivo effect of insulin on control of IRS-2 expression in liver and pancreatic islets was also

111 SP600125, did not effectively block reduced IRS-2 expression in NO donor-treated beta-cells.

112 In liver, basal IRS-2 expression is controlled via a temporal negative f

113 indings suggest that iNOS-mediated decreased IRS-2 expression may contribute to the progression and/o

114 was countered by specific glucose-regulated IRS-2 expression mediated at the transcriptional level.

115 Glucose-induced IRS-2 expression occurred in pancreatic islet beta-cells

116 Increased IRS-2 expression promotes beta-cell growth and survival,

117 -induced locomotor activity, and blockade of IRS-2 expression significantly blunts behavioral respons

118 studies showed insulin was able to suppress IRS-2 expression via activation of SREBP-1 in the liver,

119 ive insulin receptor autophosphorylation and IRS-2 expression were reduced, without changes in p42/p4

120 In the current study, we show that IRS-2 expression, but not IRS-1 expression, is positivel

121 l cytosolic [Ca2+]i prevented an increase in IRS-2 expression, indicating this was Ca2+-dependent.

122 activation of Akt in hypoxia is dependent on IRS-2 expression.

123 re significantly decreased in the absence of IRS-2 expression.

124 otein kinase B (PKB) significantly decreased IRS-2 expression.

125 regulation of insulin receptor substrate 2 (IRS-2) expression in pancreatic beta-cells is essential

126 Functionally, the elevated expression of IRS-2 facilitates breast carcinoma cell survival and inv

127 IRS-2 from db/db mouse PerMPhis also showed a 78% increa

128 in PyV-MT::Irs1(-/-) mice exhibited elevated Irs-2 function and enhanced phosphatidylinositol 3-kinas

129 molecular mechanism on how glucose regulates IRS-2 gene expression in beta-cells.

130 d glucose-induced transcriptional control of IRS-2 gene expression specific to the islet beta-cell is

131 larization demonstrated that glucose-induced IRS-2 gene expression was dependent on a rise in intrace

132 lucose (15 mM) regulation of islet beta-cell IRS-2 gene expression was rapid, with a significant incr

133 RS-2 mRNA and protein expression, as well as IRS-2 gene promoter activity, were examined in isolated

134 l hypoxia-responsive gene and establish that IRS-2 gene transcription increases in a hypoxia-inducibl

135 y reduced responses to IGF-1 in the IGF-1R-->IRS-2-->PI3K signaling pathway.

136 ed brown adipocytes in which either IRS-1 or IRS-2 has been knocked out by recombinant methods to exa

137 r results demonstrate that hepatic IRS-1 and IRS-2 have complementary roles in the control of hepatic

138 In summary, neurons containing IRS-2 immunoreactivity were identified in forebrain, mid

139 ies in the mNTS demonstrated the presence of IRS-2 in catecholamine neurons.

140 Expression of exogenous Irs-2 in Irs-2-/- cells restored the rate of glycolysis

141 estigate the specific functions of IRS-1 and IRS-2 in regulating liver function in vivo, we developed

142 on of insulin receptor substrate (IRS)-1 and IRS-2 in response to insulin.

143 that transgenic mice overexpressing IRS-1 or IRS-2 in the mammary gland showed progressive mammary hy

144 These results demonstrate that levels of IRS-2 in the VTA regulate responsiveness to the behavior

145 S-2, the authors show that overexpression of IRS-2 in the VTA results in an enhanced preference for e

146 y retroviral-mediated expression of IRS-1 or IRS-2 in their respective knockout cells.

147 ysis of the role played by signaling through IRS-2 in these brain areas.

148 celerates zebrafish embryonic growth through IRS-2 in vivo.

149 ylation of the insulin receptor substrate-2 (IRS-2) in macrophages.

150 olved in the EGF up-regulation of IRS-1, the IRS-2 induction by EGF was specifically mediated by JNK

151 Further analyses showed that both IRS-1 and IRS-2 interacted with SirT1, and the acetylation level o

152 (WT) or null for either Irs-1 (Irs-1-/-) or Irs-2 (Irs-2-/-).

153 IRS-2 is active to mediate insulin-like growth factor I-

154 of cell motility, suggesting that increased IRS-2 is essential for the EGF regulation of breast canc

155 In cancer, IRS-2 is positively associated with aggressive tumor beh

156 The IGFBP-3-induced dephosphorylation of IRS-2 is prevented by cotreatment of cells with insulin,

157 and survival, insulin receptor substrate 2 (IRS-2), is a member of a family of proteins whose inhibi

158 While wild-type, IRS-2 KO, and IRS-4 KO cells fully differentiated into m

159 increased Ser(P)-IRS-2 and decreased Tyr(P)-IRS-2 leading to reduced M2 gene expression (CD200R, CCL

160 Finally, repressing the induction of IRS-2 levels abolished the EGF enhancement of cell motil

161 The glucose-induced rise in IRS-2 levels correlated with increased IRS-2 tyrosine ph

162 kinase (PI3K) or PKB significantly increased IRS-2 levels in beta-cells.

163 -cell growth and survival, whereas decreased IRS-2 levels lead to apoptosis.

164 This glucose/IGF-1-induced decrease in IRS-2 levels was prevented by the proteasomal inhibitor,

165 on of IRS-2, which correlated with decreased IRS-2 levels.

166 In vitro, IRS-2(-/-) mammary tumor cells were less invasive and mo

167 otif phosphorylation without a difference in IRS-2 mass.

168 nique subsets of Akt substrates by Irs-1 and Irs-2 may explain their non-redundant roles in mammary t

169 cating a proteasomal mediated degradation of IRS-2 mediated via mTOR-induced Ser/Thr phosphorylation

170 ctor FoxO1 does not appear to be involved in Irs-2-mediated glycolysis.

171 from obese/diabetic db/db mice have impaired IRS-2-mediated PI3K activity and constitutively overexpr

172 f IL-1 receptor antagonist (IL-1RA) requires IRS-2-mediated PI3K activity in primary macrophages.

173 ation of Nedd4 with IRS-2, thereby enhancing IRS-2-mediated signalling and cell proliferation induced

174 communication between the IRS-1/PI3K/Akt and IRS-2/MEK/ERK pathways that coordinates AT-1 and ubiquit

175 nd growth were similar in wild-type (WT) and IRS-2(-/-) mice.

176 PyV-MT) in the mammary gland and IRS-2-null (IRS-2(-/-)) mice.

177 re closely linked to glucose homeostasis and IRS-2 more closely linked to lipid metabolism.

178 anner, reaching a maximum 4-fold increase in IRS-2 mRNA and a 5-6-fold increase in IRS-2 protein leve

179 IRS-2 mRNA and protein expression, as well as IRS-2 gene

180 Glucose (> or = 6 mM) increased IRS-2 mRNA and protein levels in a dose-dependent manner

181 inhibitor [CAIN]) abolished glucose-induced IRS-2 mRNA and protein levels, whereas expression of a c

182 Silencing IRS-2 mRNA induces insulin resistance and inhibits IFNal

183 2 insulinoma cells and mouse islets, whereas IRS-2 mRNA levels were not altered.

184 on was rapid, with a significant increase in IRS-2 mRNA levels within 2 h that reached a maximum 4-fo

185 in an iNOS-dependent manner without altering IRS-2 mRNA levels.

186 in expression in beta-cells followed that of IRS-2 mRNA.

187 brown preadipocytes, expression of IRS-1 and IRS-2 mRNAs and proteins was at relatively high levels b

188 o this selective regulation, we generated an Irs-2 mutant deficient in the recruitment of PI3K.

189 Furthermore, GRB10 associated with IRS-2, NEDD4.2 (an E3-ubiquitin ligase), IL-4Ralpha, and

190 T antigen (PyV-MT) in the mammary gland and IRS-2-null (IRS-2(-/-)) mice.

191 findings suggest a novel regulatory role of IRS-2 on the expression of IGF-IR through PKCdelta and m

192 We induced insulin resistance by silencing IRS-2 or by treating HepG2 cells with tumor necrosis fac

193 IRS-1 KO cells with IRS-1 and IRS-4, but not IRS-2 or IRS-3, compensated for the lack of differentiat

194 RNAs (shRNAs) are used to knock down IRS-1, IRS-2, or both, by 70-80% in livers of WT mice.

195 In addition, IRS-2 overexpression leads to enhanced cocaine-induced l

196 expressed low plasma insulin, reduced brain IRS-2, pAkt, and pGSK-3beta(Ser9), unchanged pPDK1, pTau

197 Thus, the IRS-2 pathway appears to be a crucial participant in the

198 IRB; insulin receptor substrate (IRS)-1 and IRS-2; phosphoinositide 3-kinase (PI3K) catalytic subuni

199 d transmembrane domain did not elicit robust IRS-2 phosphorylation in response to IL-13 suggesting th

200 IRS-2 phosphorylation was unchanged in either cell line

201 ed AGER1 and SIRT1, and altered InsR, IRS-1, IRS-2 phosphorylation, and nuclear factor kappa-light ch

202 ect of proteasome inhibitors on IL-4-induced IRS-2 phosphorylation.

203 OCS-1 overexpression preferentially inhibits IRS-2 phosphorylation.

204 icted that the gammaC tail directed enhanced IRS-2 phosphorylation.

205 n receptor and insulin receptor substrate 2 (IRS-2) phosphorylation, IRS-2-associated PI3K activity,

206 /db macrophages revealed that IL-4-dependent IRS-2/PI3K complex formation and IRS-2 tyrosine phosphor

207 ition of PI3K with wortmannin or blockage of IRS-2/PI3K complex formation with a cell permeable IRS-2

208 -3 is increased, and impaired IL-4-dependent IRS-2/PI3K formation induces a state of IL-4 resistance

209 Insulin receptor substrate 2 (IRS-2) plays a critical role in pancreatic beta-cells.

210 Insulin receptor substrate-2 (IRS-2) plays a critical role in the survival and functio

211 Insulin receptor substrate-2 (IRS-2) plays an essential role in pancreatic islet beta-

212 ology and the ability to activate PI3K, only Irs-2 positively regulates aerobic glycolysis in mammary

213 d islets, removal of the IRE decreased basal IRS-2 promoter activity in beta-cells up to 80%.

214 ly FoxO3a, not FoxO1, was capable of driving IRS-2 promoter activity via the IRE in beta-cells.

215 Consistent with this, EGF increased IRS-2 promoter activity, which was associated with recru

216 over, DLX5 was found to directly bind to the IRS-2 promoter and augmented its transcription.

217 O1 and FoxO3a associated with the IRE on the IRS-2 promoter in beta-cells in a PI3K/PKB-dependent man

218 of activated T cells (NFAT) interaction with IRS-2 promoter was analyzed by chromatin immunoprecipita

219 ption factor association with the IRE on the IRS-2 promoter was examined by chromatin immunoprecipita

220 FATc1 to conserved NFAT binding sites in the IRS-2 promoter were demonstrated.

221 In IRS-2 promoter-reporter assays conducted in isolated isl

222 at an insulin response element (IRE) on the IRS-2 promoter.

223 was marked down-regulation of IR, IRS-1, and IRS-2 protein and phosphorylation in liver; these were m

224 n with interferon-gamma (IFN-gamma), reduced IRS-2 protein expression in an iNOS-dependent manner wit

225 IRS-2 protein expression in beta-cells followed that of

226 Nonetheless, the regulation of IRS-2 protein expression in beta-cells remains largely u

227 re, we show that iNOS and NO donor decreased IRS-2 protein expression in INS-1/832 insulinoma cells a

228 n, blocked the NO donor-induced reduction in IRS-2 protein expression.

229 th the level of the Ser(1100)-phosphorylated IRS-2 protein in metastatic melanoma tissues.

230 to investigate the neuronal distribution of IRS-2 protein in rat brain.

231 ase in IRS-2 mRNA and a 5-6-fold increase in IRS-2 protein levels at > or = 12 mM glucose (p < or = 0

232 -cells expressing mTORDelta, the decrease in IRS-2 protein levels was also prevented by rapamycin or

233 -2 and the subsequent decrease in INS-1 cell IRS-2 protein levels was thwarted by the mammalian targe

234 r/Thr phosphorylation of IRS-2 and decreased IRS-2 protein levels, whereas adenoviral-mediated expres

235 /Thr phosphorylation of IRS-2 and maintained IRS-2 protein levels.

236 IRS-2 protein was also found in the ventral tegmental ar

237 of constitutively activated FOXO3a increased IRS-2 protein, MEK/ERK signaling, and UbC expression.

238 IRS-2 protein, MEK/ERK signaling, Sp1 phosphorylation, a

239 ations of four lysine residues to alanine in IRS-2 protein, on the other hand, led to its reduced bas

240 signaling pathway, through deacetylation of IRS-2 protein.

241 e domain in the catalytic loop essential for IRS-2 recognition in vitro.

242 ing insulin receptor substrate-1 (Irs-1) and Irs-2 (referred to here as double-knockout (DKO) mice) t

243 This insight into the IRS-2 regulation could provide novel therapeutic means i

244 by recombinant methods to examine IRS-1 and IRS-2 requirements for activation of aPKC.

245 d by microtubule disruption, indicating that IRS-2 requires the microtubule cytoskeleton at the level

246 ncreased blood glucose, whereas knockdown of IRS-2 resulted in the upregulation of lipogenic enzymes

247 chanism by which signaling through IRS-1 and IRS-2 results in differential outcomes, we assessed the

248 Gene disruption of IRS-2 results in failure of the beta-cell compensatory m

249 e is that our data reveal that expression of IRS-2 sensitizes breast carcinoma cells to apoptosis in

250 ked chronic insulin + high glucose-dependent IRS-2 Ser/Thr-Pro motif phosphorylation and restored IL-

251 specific subgroup of genes including IGF1R, IRS-2, SGK1, and survivin.

252 Although IRS-1 and IRS-2 share significant homology, they regulate distinct

253 as a key negative regulator of IL-4-induced IRS-2 signaling and M2 differentiation.

254 peutically manipulated to limit IL-4-induced IRS-2 signaling and polarization of M2 macrophages in al

255 our study reveals a novel mechanism by which Irs-2 signaling preferentially regulates tumor cell meta

256 ing was associated with cell growth, whereas IRS-2 signaling was associated with cell motility.

257 patic insulin receptor substrate (IRS)-1 and IRS-2 signaling, impaired activation of downstream insul

258 psilon, and impairment of insulin-stimulated IRS-2 signaling.

259 down-regulation of IGF-IR expression due to IRS-2 small interfering RNA can be compensated by overex

260 In the hypothalamus, strong IRS-2 staining was detected chiefly in the arcuate (ARC)

261 In the hindbrain, IRS-2 staining was detected in the area postrema (AP), m

262 IRS-2, STAT6, and JAK3 phosphorylation was observed in C

263 In contrast, N cells express IRS-2 that is transiently phosphorylated by IGF-I.

264 eads to increased Ser/Thr phosphorylation of IRS-2 that targets it for proteasomal degradation, resul

265 ne transfer to locally alter the activity of IRS-2, the authors show that overexpression of IRS-2 in

266 hway increases the association of Nedd4 with IRS-2, thereby enhancing IRS-2-mediated signalling and c

267 s, we assessed the contribution of IRS-1 and IRS-2 to aerobic glycolysis, which is known to impact tu

268 evidence that directly links both IRS-1 and IRS-2 to aPKC activation in immortalized brown adipocyte

269 findings reveal an important contribution of IRS-2 to breast cancer metastasis.

270 tubule cytoskeleton may facilitate access of IRS-2 to downstream effectors such as AKT.

271 te of low affinity, to specifically activate IRS-2 to levels similar to those seen with equivalent co

272 We investigated the specific contribution of IRS-2 to mammary tumor progression using transgenic mice

273 Nedd4 recruits IRS-2 to the membrane, probably through promoting Epsin1

274 inhibitor VIVIT prevented a glucose-induced IRS-2 transcription.

275 WT and IRS-2(-/-) tumors contained similar numbers of mitotic c

276 tained similar numbers of mitotic cells, but IRS-2(-/-) tumors had a higher incidence of apoptosis th

277 It was found that IRS-2 turnover in rat islet beta-cells was rapid, with m

278 IRS-2 turnover is rapid in primary beta-cells, but its e

279 se in IRS-2 levels correlated with increased IRS-2 tyrosine phosphorylation and downstream activation

280 ound that siRNA knockdown of SOCS1 prolonged IRS-2 tyrosine phosphorylation and enhanced M2 different

281 lin + high glucose did reduce IL-4-dependent IRS-2 tyrosine phosphorylation and p85 association by 54

282 4-dependent IRS-2/PI3K complex formation and IRS-2 tyrosine phosphorylation was reduced compared with

283 Proteasomal inhibition prolonged IRS-2 tyrosine phosphorylation, increased ubiquitination

284 binding, and enhances IGF-I receptor-induced IRS-2 tyrosine phosphorylation.

285 lin-stimulated insulin receptor substrate 2 (IRS-2) tyrosine phosphorylation (P < 0.05), as well as a

286 whereas MEK/ERK signaling and expression of IRS-2, UbC and AT-1 were increased.

287 Here we identify Nedd4 as an IRS-2 ubiquitin ligase.

288 IGF-I-dependent phosphorylation of IRS-1 and IRS-2 was ablated in IGFRKO cells but not in IRKO cells.

289 Within the ARC, IRS-2 was co-localized with alpha melanocyte stimulating

290 ted with SirT1, and the acetylation level of IRS-2 was down-regulated by insulin treatment.

291 ulated tyrosine phosphorylation of IRS-1 and IRS-2 was elevated, accompanied by enhanced Akt/PKB acti

292 In brown adipocytes in which either IRS-1 or IRS-2 was knocked out, insulin-induced increases in aPKC

293 Irs-2 was shown to be important for mammalian target of

294 , IRS-1(-/-) tumor cells, which express only IRS-2, were highly invasive and were resistant to apopto

295 insulin signaling proteins, i.e., IRS-1 and IRS-2, were not increased with CR, although a significan

296 phorylation of insulin receptor substrate 2 (IRS-2), whereas it had minimal effect on that of IRS-1.

297 key residue for the recognition of IRS-1 and IRS-2, whereas SOCS-1 binds to the domain in the catalyt

298 IGF-1, increased Ser/Thr phosphorylation of IRS-2, which correlated with decreased IRS-2 levels.

299 Nedd4 monoubiquitinates IRS-2, which promotes its association with Epsin1, a ubi

300 s tyrosine phosphorylation of both IRS-1 and IRS-2, while SOCS-1 overexpression preferentially inhibi