Gene Symbol: IRS-1
Description: insulin receptor substrate 1
Alias: HIRS-1, insulin receptor substrate 1, IRS-1
Species: human
Products:     IRS-1

Top Publications

  1. Rung J, Cauchi S, Albrechtsen A, Shen L, Rocheleau G, Cavalcanti Proença C, et al. Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia. Nat Genet. 2009;41:1110-5 pubmed publisher
    ..3 x 10(-12), OR = 1.19) was located adjacent to the insulin receptor substrate 1 gene (IRS1)...
  2. Lassak A, Del Valle L, Peruzzi F, Wang J, Enam S, Croul S, et al. Insulin receptor substrate 1 translocation to the nucleus by the human JC virus T-antigen. J Biol Chem. 2002;277:17231-8 pubmed
    b>Insulin receptor substrate 1 (IRS-1) is the major signaling molecule for the insulin and insulin-like growth factor I receptors, which transduces both metabolic and growth-promoting signals, and has transforming properties when ..
  3. Gual P, Baron V, Lequoy V, Van Obberghen E. Interaction of Janus kinases JAK-1 and JAK-2 with the insulin receptor and the insulin-like growth factor-1 receptor. Endocrinology. 1998;139:884-93 pubmed
  4. Tzatsos A, Kandror K. Nutrients suppress phosphatidylinositol 3-kinase/Akt signaling via raptor-dependent mTOR-mediated insulin receptor substrate 1 phosphorylation. Mol Cell Biol. 2006;26:63-76 pubmed
    ..signaling via Raptor-dependent mTOR (mammalian target of rapamycin)-mediated phosphorylation of insulin receptor substrate 1 (IRS-1)...
  5. Slattery M, Sweeney C, Wolff R, Herrick J, Baumgartner K, Giuliano A, et al. Genetic variation in IGF1, IGFBP3, IRS1, IRS2 and risk of breast cancer in women living in Southwestern United States. Breast Cancer Res Treat. 2007;104:197-209 pubmed
    ..Our data suggest that associations between insulin-related genes and breast cancer risk among women living in the Southwestern United States may be dependent on estrogen exposure and may differ by ethnicity. ..
  6. Mousavinasab F, Tähtinen T, Jokelainen J, Koskela P, Vanhala M, Oikarinen J, et al. Common polymorphisms in the PPARgamma2 and IRS-1 genes and their interaction influence serum adiponectin concentration in young Finnish men. Mol Genet Metab. 2005;84:344-8 pubmed
    ..We conclude that the Ala12Ala genotype of PPARgamma2 is associated with elevated adiponectin level, and that the PPARgamma2 and IRS-1 genes have a possible interaction in their effects on adiponectin concentration. ..
  7. Laukkanen O, Pihlajamaki J, Lindstrom J, Eriksson J, Valle T, Hamalainen H, et al. Common polymorphisms in the genes regulating the early insulin signalling pathway: effects on weight change and the conversion from impaired glucose tolerance to Type 2 diabetes. The Finnish Diabetes Prevention Study. Diabetologia. 2004;47:871-7 pubmed
  8. Dearth R, Cui X, Kim H, Kuiatse I, Lawrence N, Zhang X, et al. Mammary tumorigenesis and metastasis caused by overexpression of insulin receptor substrate 1 (IRS-1) or IRS-2. Mol Cell Biol. 2006;26:9302-14 pubmed
    ..This study defines IRSs as oncogene proteins in vivo and provides new models to develop inhibitors against IRSs for anticancer therapy. ..
  9. Tok E, Ertunc D, Bilgin O, Erdal E, Kaplanoglu M, Dilek S. Association of insulin receptor substrate-1 G972R variant with baseline characteristics of the patients with gestational diabetes mellitus. Am J Obstet Gynecol. 2006;194:868-72 pubmed
    ..IRS-1 G972R was associated with the baseline characteristics of the patients with GDM, and might be related to insulin resistance that is seen in obese patients with GDM. ..

More Information


  1. Perez M, Tellechea M, Aranguren F, Taverna M, Rodríguez R, Meroño T, et al. The rs1801278 G>A polymorphism of IRS-1 is associated with metabolic syndrome in healthy nondiabetic men. Modulation by cigarette smoking status. Diabetes Res Clin Pract. 2011;93:e95-7 pubmed publisher
    ..rs1801278 G>A was genotyped in 610 healthy Argentinian men. GA carriers had lower risk of MS (OR=0.52, P=0.045), particularly among smokers (OR=0.10, P=0.006). rs1801278 GA carriers had lower risk of MS, especially among smokers. ..
  2. Jellema A, Zeegers M, Feskens E, Dagnelie P, Mensink R. Gly972Arg variant in the insulin receptor substrate-1 gene and association with Type 2 diabetes: a meta-analysis of 27 studies. Diabetologia. 2003;46:990-5 pubmed
    ..The odds ratios are generally higher in hospital-based studies, including relatively young, symptomatic, cases. ..
  3. Morelli C, Garofalo C, Sisci D, del Rincon S, Cascio S, Tu X, et al. Nuclear insulin receptor substrate 1 interacts with estrogen receptor alpha at ERE promoters. Oncogene. 2004;23:7517-26 pubmed
    b>Insulin receptor substrate 1 (IRS-1) is a major signaling molecule activated by the insulin and insulin-like growth factor I receptors...
  4. Farhang Fallah J, Yin X, Trentin G, Cheng A, Rozakis Adcock M. Cloning and characterization of PHIP, a novel insulin receptor substrate-1 pleckstrin homology domain interacting protein. J Biol Chem. 2000;275:40492-7 pubmed
    ..We conclude that PHIP represents a novel protein ligand of the IRS-1 PH domain that may serve to link IRS-1 to the insulin receptor. ..
  5. Yin Y, Yan Z, Lu N, Xu Q, He J, Qian X, et al. Downregulation of miR-145 associated with cancer progression and VEGF transcriptional activation by targeting N-RAS and IRS1. Biochim Biophys Acta. 2013;1829:239-47 pubmed publisher
  6. Sweeney C, Murtaugh M, Baumgartner K, Byers T, Giuliano A, Herrick J, et al. Insulin-like growth factor pathway polymorphisms associated with body size in Hispanic and non-Hispanic white women. Cancer Epidemiol Biomarkers Prev. 2005;14:1802-9 pubmed
    ..These results provide evidence that IGF pathway polymorphisms have functional effects on growth and central obesity and indicate that genotype-phenotype relationships are ethnic specific. ..
  7. Greene M, Morrice N, Garofalo R, Roth R. Modulation of human insulin receptor substrate-1 tyrosine phosphorylation by protein kinase Cdelta. Biochem J. 2004;378:105-16 pubmed
    ..These results indicate that PKCdelta modulates the ability of the insulin receptor to tyrosine-phosphorylate IRS-1 by direct phosphorylation of the IRS-1 molecule. ..
  8. Zhang J, Gao Z, Yin J, Quon M, Ye J. S6K directly phosphorylates IRS-1 on Ser-270 to promote insulin resistance in response to TNF-(alpha) signaling through IKK2. J Biol Chem. 2008;283:35375-82 pubmed publisher
    ..We present a new mechanism for TNF-alpha to induce insulin resistance that involves activation of S6K by an IKK2-dependent pathway. S6K directly phosphorylates IRS-1 on multiple serine residues to inhibit insulin signaling. ..
  9. Jellema A, Mensink R, Kromhout D, Saris W, Feskens E. Metabolic risk markers in an overweight and normal weight population with oversampling of carriers of the IRS-1 972Arg-variant. Atherosclerosis. 2003;171:75-81 pubmed
    ..The impact of this genotype and its modification by overweight may be smaller than suggested previously. ..
  10. Skolnik E, Lee C, Batzer A, Vicentini L, Zhou M, Daly R, et al. The SH2/SH3 domain-containing protein GRB2 interacts with tyrosine-phosphorylated IRS1 and Shc: implications for insulin control of ras signalling. EMBO J. 1993;12:1929-36 pubmed
    ..These interactions may play a crucial role in activation of p21ras and the control of downstream effector molecules. ..
  11. Ozes O, Akca H, Mayo L, Gustin J, Maehama T, Dixon J, et al. A phosphatidylinositol 3-kinase/Akt/mTOR pathway mediates and PTEN antagonizes tumor necrosis factor inhibition of insulin signaling through insulin receptor substrate-1. Proc Natl Acad Sci U S A. 2001;98:4640-5 pubmed
    ..These results suggest that TNF impairs insulin signaling through IRS-1 by activation of a PI 3-kinase/Akt/mTOR pathway, which is antagonized by PTEN. ..
  12. Shah O, Hunter T. Turnover of the active fraction of IRS1 involves raptor-mTOR- and S6K1-dependent serine phosphorylation in cell culture models of tuberous sclerosis. Mol Cell Biol. 2006;26:6425-34 pubmed
  13. Rui L, Yuan M, Frantz D, Shoelson S, White M. SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2. J Biol Chem. 2002;277:42394-8 pubmed
    ..Thus, SOCS-mediated degradation of IRS proteins, presumably via the elongin BC ubiquitin-ligase, might be a general mechanism of inflammation-induced insulin resistance, providing a target for therapy. ..
  14. Ravichandran L, Esposito D, Chen J, Quon M. Protein kinase C-zeta phosphorylates insulin receptor substrate-1 and impairs its ability to activate phosphatidylinositol 3-kinase in response to insulin. J Biol Chem. 2001;276:3543-9 pubmed
  15. Morini E, Prudente S, Succurro E, Chandalia M, Zhang Y, Mammarella S, et al. IRS1 G972R polymorphism and type 2 diabetes: a paradigm for the difficult ascertainment of the contribution to disease susceptibility of 'low-frequency-low-risk' variants. Diabetologia. 2009;52:1852-7 pubmed publisher
    ..Our data suggest that focusing on early-onset diabetes, which is characterised by a stronger genetic background, may be part of such a strategy. ..
  16. Federici M, Pandolfi A, De Filippis E, Pellegrini G, Menghini R, Lauro D, et al. G972R IRS-1 variant impairs insulin regulation of endothelial nitric oxide synthase in cultured human endothelial cells. Circulation. 2004;109:399-405 pubmed
  17. Fallucca F, Dalfrà M, Sciullo E, Masin M, Buongiorno A, Napoli A, et al. Polymorphisms of insulin receptor substrate 1 and beta3-adrenergic receptor genes in gestational diabetes and normal pregnancy. Metabolism. 2006;55:1451-6 pubmed
    ..We studied possible relations between GDM and both insulin receptor substrate 1 (IRS-1) (Gly972Arg) and beta3-adrenergic receptor (ADRB3 Trp64Arg, beta3-AR) gene mutations, considered ..
  18. Wagner K, Hemminki K, Grzybowska E, Klaes R, Butkiewicz D, Pamula J, et al. The insulin-like growth factor-1 pathway mediator genes: SHC1 Met300Val shows a protective effect in breast cancer. Carcinogenesis. 2004;25:2473-8 pubmed
    ..54, 95% CI 0.32-0.89, P = 0.01). A genotype combination analysis of the non-synonymous polymorphisms in the IRS1, IRS2 and SHC1 genes did not show any effect on breast cancer risk. ..
  19. Esposito D, Aru F, Lattanzio R, Morgano A, Abbondanza M, Malekzadeh R, et al. The insulin receptor substrate 1 (IRS1) in intestinal epithelial differentiation and in colorectal cancer. PLoS ONE. 2012;7:e36190 pubmed publisher
    ..cancer (CRC) is associated with lifestyle factors that affect insulin/IGF signaling, of which the insulin receptor substrate 1 (IRS1) is a key transducer...
  20. Ericson U, Rukh G, Stojkovic I, Sonestedt E, Gullberg B, Wirfalt E, et al. Sex-specific interactions between the IRS1 polymorphism and intakes of carbohydrates and fat on incident type 2 diabetes. Am J Clin Nutr. 2013;97:208-16 pubmed publisher
    The minor T allele of rs2943641 near the gene encoding for insulin receptor substrate 1 (IRS1) has been associated with decreased risk of type 2 diabetes (T2D) and adiposity in genome-wide association studies...
  21. Hribal M, Federici M, Porzio O, Lauro D, Borboni P, Accili D, et al. The Gly-->Arg972 amino acid polymorphism in insulin receptor substrate-1 affects glucose metabolism in skeletal muscle cells. J Clin Endocrinol Metab. 2000;85:2004-13 pubmed
    ..The present data indicate that the polymorphism at codon 972 of IRS-1 may contribute to the in vivo insulin resistance observed in carriers of this variant. ..
  22. Esposito D, Li Y, Vanni C, Mammarella S, Veschi S, Della Loggia F, et al. A novel T608R missense mutation in insulin receptor substrate-1 identified in a subject with type 2 diabetes impairs metabolic insulin signaling. J Clin Endocrinol Metab. 2003;88:1468-75 pubmed
    ..We conclude that a naturally occurring substitution of Arg for Thr(608) in IRS-1 is a rare human mutation that may contribute to insulin resistance by impairing metabolic signaling through PI 3-kinase-dependent pathways. ..
  23. Hribal M, Tornei F, Pujol A, Menghini R, Barcaroli D, Lauro D, et al. Transgenic mice overexpressing human G972R IRS-1 show impaired insulin action and insulin secretion. J Cell Mol Med. 2008;12:2096-106 pubmed publisher
    ..Furthermore, they may become an important tool to test novel tailored therapies. ..
  24. Chang Q, Li Y, White M, Fletcher J, Xiao S. Constitutive activation of insulin receptor substrate 1 is a frequent event in human tumors: therapeutic implications. Cancer Res. 2002;62:6035-8 pubmed
    b>Insulin receptor substrate 1 (IRS-1) is a major substrate of insulin, insulin-like growth factors, and cytokine signaling and plays an important role in mediating apoptosis, cell differentiation, and cell transformation...
  25. Kilpeläinen T, Zillikens M, Stancakova A, Finucane F, Ried J, Langenberg C, et al. Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile. Nat Genet. 2011;43:753-60 pubmed publisher
    ..Our findings provide new insights into adiposity and insulin resistance. ..
  26. Ehrmann D, Tang X, Yoshiuchi I, Cox N, Bell G. Relationship of insulin receptor substrate-1 and -2 genotypes to phenotypic features of polycystic ovary syndrome. J Clin Endocrinol Metab. 2002;87:4297-300 pubmed
    ..Thus, individuals with the common IRS-2 Gly/Gly genotype may be at increased risk of developing type 2 diabetes. ..
  27. Slattery M, Samowitz W, Curtin K, Ma K, Hoffman M, Caan B, et al. Associations among IRS1, IRS2, IGF1, and IGFBP3 genetic polymorphisms and colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2004;13:1206-14 pubmed
    ..These data suggest that the insulin-related pathway may be important in the etiology of colon cancer but not rectal cancer. ..
  28. Sun X, Rothenberg P, Kahn C, Backer J, Araki E, Wilden P, et al. Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein. Nature. 1991;352:73-7 pubmed
    ..Thus IRS-1 may link the insulin receptor kinase and enzymes regulating cellular growth and metabolism. ..
  29. Federici M, Petrone A, Porzio O, Bizzarri C, Lauro D, D Alfonso R, et al. The Gly972-->Arg IRS-1 variant is associated with type 1 diabetes in continental Italy. Diabetes. 2003;52:887-90 pubmed
    ..49 +/- 0.058, n = 34, and 0.76 +/- 0.066, n = 134, respectively [means +/- SE]; P = 0.051). Our findings suggest a role for Arg(972) IRS-1 in conferring risk for the development of type 1 diabetes. ..
  30. Marini M, Frontoni S, Mineo D, Bracaglia D, Cardellini M, De Nicolais P, et al. The Arg972 variant in insulin receptor substrate-1 is associated with an atherogenic profile in offspring of type 2 diabetic patients. J Clin Endocrinol Metab. 2003;88:3368-71 pubmed
    ..These results suggest that the Arg(972) IRS-1 variant could contribute to the risk for atherosclerotic cardiovascular diseases associated with type 2 diabetes by producing a cluster of insulin resistance-related metabolic abnormalities. ..
  31. Ma Z, Gibson S, Byrne M, Zhang J, White M, Shaw L. Suppression of insulin receptor substrate 1 (IRS-1) promotes mammary tumor metastasis. Mol Cell Biol. 2006;26:9338-51 pubmed
    ..Collectively, our findings reveal that inactivation of IRS-1 enhances breast cancer metastasis and support the novel hypothesis that IRS-1 has metastasis suppressor functions for breast cancer. ..
  32. Lee Y, Giraud J, Davis R, White M. c-Jun N-terminal kinase (JNK) mediates feedback inhibition of the insulin signaling cascade. J Biol Chem. 2003;278:2896-902 pubmed
    ..cytokines inhibits insulin signaling, at least in part, by stimulating phosphorylation of rat/mouse insulin receptor substrate 1 (Irs1) at Ser(307) (Ser(312) in human IRS1)...
  33. Witchel S, Smith R, Tomboc M, Aston C. Candidate gene analysis in premature pubarche and adolescent hyperandrogenism. Fertil Steril. 2001;75:724-30 pubmed
    ..This approach offers a novel paradigm to investigate and identify the genetic factors relevant to polycystic ovary syndrome. ..
  34. Baroni M, Leonetti F, Sentinelli F, Romeo S, Filippi E, Fanelli M, et al. The G972R variant of the insulin receptor substrate-1 (IRS-1) gene is associated with insulin resistance in "uncomplicated" obese subjects evaluated by hyperinsulinemic-euglycemic clamp. J Endocrinol Invest. 2004;27:754-9 pubmed
  35. Dearth R, Cui X, Kim H, Hadsell D, Lee A. Oncogenic transformation by the signaling adaptor proteins insulin receptor substrate (IRS)-1 and IRS-2. Cell Cycle. 2007;6:705-13 pubmed
    ..In this review we will discuss the role of IRSs in both transformation and cancer progression. ..
  36. Aguirre V, Werner E, Giraud J, Lee Y, Shoelson S, White M. Phosphorylation of Ser307 in insulin receptor substrate-1 blocks interactions with the insulin receptor and inhibits insulin action. J Biol Chem. 2002;277:1531-7 pubmed
    ..These results suggest that inhibition of PTB domain function in IRS-1 by phosphorylation of Ser(307) (Ser(312) in human IRS-1) might be a general mechanism to regulate insulin signaling. ..
  37. Giorgetti Peraldi S, Peyrade F, Baron V, Van Obberghen E. Involvement of Janus kinases in the insulin signaling pathway. Eur J Biochem. 1995;234:656-60 pubmed
    ..In conclusion, our results suggest that the JAK proteins could participate in insulin signal transduction, and could therefore constitute an alternative pathway for mediating some of the pleiotropic responses induced by insulin. ..
  38. El Mkadem S, Lautier C, Macari F, Molinari N, Lefebvre P, Renard E, et al. Role of allelic variants Gly972Arg of IRS-1 and Gly1057Asp of IRS-2 in moderate-to-severe insulin resistance of women with polycystic ovary syndrome. Diabetes. 2001;50:2164-8 pubmed
    ..0085, OR 1.7, 95% CI 1.09-2.99). We conclude that polymorphic alleles of both IRS-1 and IRS-2, alone or in combination, may have a functional impact on the insulin-resistant component of PCOS. ..
  39. Gibson S, Ma Z, Shaw L. Divergent roles for IRS-1 and IRS-2 in breast cancer metastasis. Cell Cycle. 2007;6:631-7 pubmed
    ..Understanding how the IRS proteins function in tumor progression is essential for future efforts aimed at developing approaches to target IRS-1 and IRS-2 in a diagnostic or therapeutic manner for the benefit of breast cancer patients. ..
  40. Almind K, Bjørbaek C, Vestergaard H, Hansen T, Echwald S, Pedersen O. Aminoacid polymorphisms of insulin receptor substrate-1 in non-insulin-dependent diabetes mellitus. Lancet. 1993;342:828-32 pubmed
    ..Our results suggest that aminoacid polymorphisms in IRS-1 may be involved in the aetiology of a subset of late-onset NIDDM. ..
  41. Pappa K, Gazouli M, Economou K, Daskalakis G, Anastasiou E, Anagnou N, et al. Gestational diabetes mellitus shares polymorphisms of genes associated with insulin resistance and type 2 diabetes in the Greek population. Gynecol Endocrinol. 2011;27:267-72 pubmed publisher
    ..Thus, our data suggest that the common T2D susceptibility polymorphism of TCF7L2 (rs7903146 C/T) gene, and the G972R polymorphism of the IRS1 gene, seem to predispose to GDM in Greek women. ..
  42. Shi B, Sepp Lorenzino L, Prisco M, Linsley P, deAngelis T, Baserga R. Micro RNA 145 targets the insulin receptor substrate-1 and inhibits the growth of colon cancer cells. J Biol Chem. 2007;282:32582-90 pubmed
    ..Taken together, these results identify miR145 as a micro RNA that down-regulates the IRS-1 protein, and inhibits the growth of human cancer cells. ..
  43. Burguete Garcia A, Cruz Lopez M, Madrid Marina V, Lopez Ridaura R, Hernandez Avila M, Cortina B, et al. Association of Gly972Arg polymorphism of IRS1 gene with type 2 diabetes mellitus in lean participants of a national health survey in Mexico: a candidate gene study. Metabolism. 2010;59:38-45 pubmed publisher
    ..The restriction of including only participants with normal BMI might increase the power to detect genetic determinants of T2D. ..
  44. Ogihara T, Isobe T, Ichimura T, Taoka M, Funaki M, Sakoda H, et al. 14-3-3 protein binds to insulin receptor substrate-1, one of the binding sites of which is in the phosphotyrosine binding domain. J Biol Chem. 1997;272:25267-74 pubmed
    ..Thus, the association with 14-3-3 protein may play a role in the regulation of insulin sensitivity by interrupting the association between the insulin receptor and IRS-1. ..
  45. Florez J, Sjögren M, Burtt N, Orho Melander M, Schayer S, Sun M, et al. Association testing in 9,000 people fails to confirm the association of the insulin receptor substrate-1 G972R polymorphism with type 2 diabetes. Diabetes. 2004;53:3313-8 pubmed
    ..15 [1.05-1.26], P = 0.001). Despite genotyping 9,000 people and >95% power to reproduce the estimated OR from the recent meta-analysis, we were unable to replicate the association of the IRS-1 G972R polymorphism with type 2 diabetes. ..
  46. Gual P, Gonzalez T, Gremeaux T, Barres R, Le Marchand Brustel Y, Tanti J. Hyperosmotic stress inhibits insulin receptor substrate-1 function by distinct mechanisms in 3T3-L1 adipocytes. J Biol Chem. 2003;278:26550-7 pubmed
    ..On the other hand, prolonged osmotic stress alters IRS-1 function by inducing its degradation, which could contribute to the down-regulation of insulin action. ..
  47. Huang C, Lin Z, Zhou Y, Fang M, Sun S, Jiang W, et al. Arg(972) insulin receptor substrate-1 is associated with elevated plasma endothelin-1 level in hypertensives. J Hypertens. 2012;30:1751-7 pubmed publisher
    ..This study for the first time provides insights into the role of Arg(972) IRS-1 in hypertension. ..
  48. Tang Y, Han X, Sun X, Lv C, Zhang X, Guo W, et al. Association study of a common variant near IRS1 with type 2 diabetes mellitus in Chinese Han population. Endocrine. 2013;43:84-91 pubmed publisher
    ..Our study was not able to demonstrate the association between rs2943641 near IRS1 and T2DM in a Chinese Han population. However, this SNP may be associated with postprandial hyperglycemia. ..
  49. Tseng Y, Kriauciunas K, Kokkotou E, Kahn C. Differential roles of insulin receptor substrates in brown adipocyte differentiation. Mol Cell Biol. 2004;24:1918-29 pubmed
    ..Although IRS-4 is not essential for the process, overexpression of IRS-4 can compensate for the deficiency in differentiation in IRS-1 KO cells. ..
  50. Zhang J, Du Y, Lin Y, Chen Y, Yang L, Wang H, et al. The cell growth suppressor, mir-126, targets IRS-1. Biochem Biophys Res Commun. 2008;377:136-40 pubmed publisher
    ..In conclusion, we developed a simple method for high-throughput screening of miRNAs and found that mir-126, a cell growth suppressor, targets IRS-1. ..
  51. Baroni M, Arca M, Sentinelli F, Buzzetti R, Capici F, Lovari S, et al. The G972R variant of the insulin receptor substrate-1 (IRS-1) gene, body fat distribution and insulin-resistance. Diabetologia. 2001;44:367-72 pubmed
    ..These findings indicate a possible interaction between the IRS-1 variant and obesity in worsening insulin sensitivity. ..
  52. McGettrick A, Feener E, Kahn C. Human insulin receptor substrate-1 (IRS-1) polymorphism G972R causes IRS-1 to associate with the insulin receptor and inhibit receptor autophosphorylation. J Biol Chem. 2005;280:6441-6 pubmed
  53. Bommer G, Feng Y, Iura A, Giordano T, Kuick R, Kadikoy H, et al. IRS1 regulation by Wnt/beta-catenin signaling and varied contribution of IRS1 to the neoplastic phenotype. J Biol Chem. 2010;285:1928-38 pubmed publisher
    ..Based on the results of microarray-based gene expression profiling we found the insulin receptor substrate 1 (IRS1) gene as one of the most highly up-regulated genes upon ectopic expression of a mutant, ..
  54. Marin C, Perez Martinez P, Delgado Lista J, Gomez P, Rodriguez F, Yubero Serrano E, et al. The insulin sensitivity response is determined by the interaction between the G972R polymorphism of the insulin receptor substrate 1 gene and dietary fat. Mol Nutr Food Res. 2011;55:328-35 pubmed publisher
    ..The aim of this study was to explore the influence of the G972R polymorphism at the insulin receptor substrate 1 gene on insulin sensitivity in a healthy young population...
  55. Gao Z, Hwang D, Bataille F, Lefevre M, York D, Quon M, et al. Serine phosphorylation of insulin receptor substrate 1 by inhibitor kappa B kinase complex. J Biol Chem. 2002;277:48115-21 pubmed
  56. Greene M, Sakaue H, Wang L, Alessi D, Roth R. Modulation of insulin-stimulated degradation of human insulin receptor substrate-1 by Serine 312 phosphorylation. J Biol Chem. 2003;278:8199-211 pubmed
    ..In summary, our results indicate that the insulin-stimulated degradation of IRS-1 via the phosphatidylinositol 3-kinase pathway is in part dependent upon the Ser(312) phosphorylation of IRS-1. ..
  57. Morelli C, Garofalo C, Bartucci M, Surmacz E. Estrogen receptor-alpha regulates the degradation of insulin receptor substrates 1 and 2 in breast cancer cells. Oncogene. 2003;22:4007-16 pubmed
    In breast cancer cells, 17-beta-estradiol (E2) upregulates the expression of insulin receptor substrate 1 (IRS-1), a molecule transmitting insulin-like growth factor-I (IGF-I) signals through the PI-3K/Akt survival pathways...
  58. Xu X, Sarikas A, Dias Santagata D, Dolios G, Lafontant P, Tsai S, et al. The CUL7 E3 ubiquitin ligase targets insulin receptor substrate 1 for ubiquitin-dependent degradation. Mol Cell. 2008;30:403-14 pubmed publisher
    ..In this report, we identified insulin receptor substrate 1 (IRS-1), a critical mediator of the insulin/insulin-like growth factor 1 signaling, as a proteolytic ..
  59. Del Rincón S, Guo Q, Morelli C, Shiu H, Surmacz E, Miller W. Retinoic acid mediates degradation of IRS-1 by the ubiquitin-proteasome pathway, via a PKC-dependant mechanism. Oncogene. 2004;23:9269-79 pubmed
    ..Together, these results indicate that RA regulates IRS-1 levels by the ubiquitin-proteasome pathway, involving a PKC-sensitive mechanism. ..
  60. van Dam R, Hoebee B, Seidell J, Schaap M, Blaak E, Feskens E. The insulin receptor substrate-1 Gly972Arg polymorphism is not associated with Type 2 diabetes mellitus in two population-based studies. Diabet Med. 2004;21:752-8 pubmed
    ..Our findings indicate that the IRS-1 Gly972Arg variant does not substantially increase risk of common Type 2 diabetes, or Type 2 diabetes in obese persons. ..
  61. Lee A, Gooch J, Oesterreich S, Guler R, Yee D. Insulin-like growth factor I-induced degradation of insulin receptor substrate 1 is mediated by the 26S proteasome and blocked by phosphatidylinositol 3'-kinase inhibition. Mol Cell Biol. 2000;20:1489-96 pubmed
    b>Insulin receptor substrate 1 (IRS-1) is a critical adapter protein involved in both insulin and insulin-like growth factor (IGF) signaling...
  62. Zeggini E, Parkinson J, Halford S, Owen K, Frayling T, Walker M, et al. Association studies of insulin receptor substrate 1 gene (IRS1) variants in type 2 diabetes samples enriched for family history and early age of onset. Diabetes. 2004;53:3319-22 pubmed
  63. Baserga R. The insulin receptor substrate-1: a biomarker for cancer?. Exp Cell Res. 2009;315:727-32 pubmed publisher
    ..In addition, I would like to propose that IRS-1 may have a more general role in cancer, and could be considered as a protein having the opposite effect of tumor suppressors, a sort of anti-p53 molecule. ..
  64. Esposito D, Li Y, Cama A, Quon M. Tyr(612) and Tyr(632) in human insulin receptor substrate-1 are important for full activation of insulin-stimulated phosphatidylinositol 3-kinase activity and translocation of GLUT4 in adipose cells. Endocrinology. 2001;142:2833-40 pubmed
    ..Overexpression of IRS1-Y612 or IRS1-Y632 caused intermediate effects. Thus, both Tyr(612) and Tyr(632) are important for IRS-1 to fully activate PI3K and mediate translocation of GLUT4 in response to insulin. ..
  65. Andreozzi F, Laratta E, Sciacqua A, Perticone F, Sesti G. Angiotensin II impairs the insulin signaling pathway promoting production of nitric oxide by inducing phosphorylation of insulin receptor substrate-1 on Ser312 and Ser616 in human umbilical vein endothelial cells. Circ Res. 2004;94:1211-8 pubmed
  66. Aguirre V, Uchida T, Yenush L, Davis R, White M. The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307). J Biol Chem. 2000;275:9047-54 pubmed
    ..These results suggest that phosphorylation of serine 307 might mediate, at least partially, the inhibitory effect of proinflammatory cytokines like TNFalpha on IRS-1 function. ..