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IRS2

{{Short description|Protein-coding gene in the species Homo sapiens}}

{{Infobox_gene}}

{{For|chemical compound with molecular formula IrS2|Iridium disulfide}}

Insulin receptor substrate 2 is a protein that in humans is encoded by the IRS2 gene.{{cite journal |vauthors=Ogihara T, Isobe T, Ichimura T, Taoka M, Funaki M, Sakoda H, Onishi Y, Inukai K, Anai M, Fukushima Y, Kikuchi M, Yazaki Y, Oka Y, Asano T | title = 14-3-3 protein binds to insulin receptor substrate-1, one of the binding sites of which is in the phosphotyrosine binding domain | journal = J Biol Chem | volume = 272 | issue = 40 | pages = 25267–74 |date=Oct 1997 | pmid = 9312143 | doi =10.1074/jbc.272.40.25267 | doi-access = free }}

Function

This gene encodes the insulin receptor substrate 2, a cytoplasmic signaling molecule that mediates effects of insulin, insulin-like growth factor 1, and other cytokines by acting as a molecular adaptor between diverse receptor tyrosine kinases and downstream effectors. The product of this gene is phosphorylated by the insulin receptor tyrosine kinase upon receptor stimulation, as well as by an interleukin 4 receptor-associated kinase in response to IL4 treatment.{{cite web | title = Entrez Gene: IRS2 insulin receptor substrate 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8660}}

Mice lacking IRS2 have a diabetic phenotype{{cite journal |vauthors=Lin X, Taguchi A, Park S, Kushner JA, Li F, Li Y, White MF | title = Dysregulation of insulin receptor substrate 2 in beta cells and brain causes obesity and diabetes | journal = J. Clin. Invest. | volume = 114 | issue = 7 | pages = 908–16 |date=October 2004 | pmid = 15467829 | pmc = 518668 | doi = 10.1172/JCI22217 }} as well as a 40% reduction in brain mass.{{cite journal |vauthors=Schubert M, Brazil DP, Burks DJ, Kushner JA, Ye J, Flint CL, Farhang-Fallah J, Dikkes P, Warot XM, Rio C, Corfas G, White MF | title = Insulin receptor substrate-2 deficiency impairs brain growth and promotes tau phosphorylation | journal = J. Neurosci. | volume = 23 | issue = 18 | pages = 7084–92 |date=August 2003 | pmid = 12904469 | pmc = 6740672 | doi = 10.1523/JNEUROSCI.23-18-07084.2003}}

Interactions

IRS2 has been shown to interact with:

  • PLCG1,{{cite journal |vauthors=Sozzani P, Hasan L, Séguélas MH, Caput D, Ferrara P, Pipy B, Cambon C | title = IL-13 induces tyrosine phosphorylation of phospholipase C gamma-1 following IRS-2 association in human monocytes: relationship with the inhibitory effect of IL-13 on ROI production | journal = Biochem. Biophys. Res. Commun. | volume = 244 | issue = 3 | pages = 665–70 |date=March 1998 | pmid = 9535722 | doi = 10.1006/bbrc.1998.8314 }}
  • SOCS1,{{cite journal |vauthors=Rui L, Yuan M, Frantz D, Shoelson S, White MF | title = SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2 | journal = J. Biol. Chem. | volume = 277 | issue = 44 | pages = 42394–8 |date=November 2002 | pmid = 12228220 | doi = 10.1074/jbc.C200444200 | doi-access = free }} and
  • PIK3R1,{{cite journal |vauthors=Argetsinger LS, Norstedt G, Billestrup N, White MF, Carter-Su C | title = Growth hormone, interferon-gamma, and leukemia inhibitory factor utilize insulin receptor substrate-2 in intracellular signaling | journal = J. Biol. Chem. | volume = 271 | issue = 46 | pages = 29415–21 |date=November 1996 | pmid = 8910607 | doi = 10.1074/jbc.271.46.29415 | doi-access = free }}{{cite journal |vauthors=Verdier F, Chrétien S, Billat C, Gisselbrecht S, Lacombe C, Mayeux P | title = Erythropoietin induces the tyrosine phosphorylation of insulin receptor substrate-2. An alternate pathway for erythropoietin-induced phosphatidylinositol 3-kinase activation | journal = J. Biol. Chem. | volume = 272 | issue = 42 | pages = 26173–8 |date=October 1997 | pmid = 9334184 | doi = 10.1074/jbc.272.42.26173 | doi-access = free }}{{cite journal |vauthors=Kim B, Cheng HL, Margolis B, Feldman EL | title = Insulin receptor substrate 2 and Shc play different roles in insulin-like growth factor I signaling | journal = J. Biol. Chem. | volume = 273 | issue = 51 | pages = 34543–50 |date=December 1998 | pmid = 9852124 | doi = 10.1074/jbc.273.51.34543 | doi-access = free }}{{cite journal |vauthors=Hamer I, Foti M, Emkey R, Cordier-Bussat M, Philippe J, De Meyts P, Maeder C, Kahn CR, Carpentier JL | title = An arginine to cysteine(252) mutation in insulin receptors from a patient with severe insulin resistance inhibits receptor internalisation but preserves signalling events | journal = Diabetologia | volume = 45 | issue = 5 | pages = 657–67 |date=May 2002 | pmid = 12107746 | doi = 10.1007/s00125-002-0798-5 | doi-access = free }}

References

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Further reading

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  • {{cite journal | author=White MF |title=The IRS-signalling system: a network of docking proteins that mediate insulin action. |journal=Mol. Cell. Biochem. |volume=182 |issue= 1–2 |pages= 3–11 |year= 1999 |pmid= 9609109 |doi=10.1023/A:1006806722619 |s2cid=32623861 }}
  • {{cite journal |vauthors=Jiang H, Harris MB, Rothman P |title=IL-4/IL-13 signaling beyond JAK/STAT. |journal=J. Allergy Clin. Immunol. |volume=105 |issue= 6 Pt 1 |pages= 1063–70 |year= 2000 |pmid= 10856136 |doi=10.1067/mai.2000.107604 |doi-access=free }}
  • {{cite journal |vauthors=Sesti G, Federici M, Hribal ML, etal |title=Defects of the insulin receptor substrate (IRS) system in human metabolic disorders. |journal=FASEB J. |volume=15 |issue= 12 |pages= 2099–111 |year= 2001 |pmid= 11641236 |doi= 10.1096/fj.01-0009rev |s2cid=6429338 |doi-access=free }}
  • {{cite journal |vauthors=Gibson SL, Ma Z, Shaw LM |title=Divergent roles for IRS-1 and IRS-2 in breast cancer metastasis. |journal=Cell Cycle |volume=6 |issue= 6 |pages= 631–7 |year= 2007 |pmid= 17361103 |doi= 10.4161/cc.6.6.3987|doi-access=free }}
  • {{cite journal |vauthors=Dearth RK, Cui X, Kim HJ, etal |title=Oncogenic transformation by the signaling adaptor proteins insulin receptor substrate (IRS)-1 and IRS-2. |journal=Cell Cycle |volume=6 |issue= 6 |pages= 705–13 |year= 2007 |pmid= 17374994 |doi= 10.4161/cc.6.6.4035|doi-access=free }}
  • {{cite journal |vauthors=Johnston JA, Wang LM, Hanson EP, etal |title=Interleukins 2, 4, 7, and 15 stimulate tyrosine phosphorylation of insulin receptor substrates 1 and 2 in T cells. Potential role of JAK kinases. |journal=J. Biol. Chem. |volume=270 |issue= 48 |pages= 28527–30 |year= 1996 |pmid= 7499365 |doi=10.1074/jbc.270.48.28527 |doi-access=free }}
  • {{cite journal |vauthors=Patti ME, Sun XJ, Bruening JC, etal |title=4PS/insulin receptor substrate (IRS)-2 is the alternative substrate of the insulin receptor in IRS-1-deficient mice. |journal=J. Biol. Chem. |volume=270 |issue= 42 |pages= 24670–3 |year= 1995 |pmid= 7559579 |doi=10.1074/jbc.270.42.24670 |doi-access=free }}
  • {{cite journal |vauthors=Sun XJ, Wang LM, Zhang Y, etal |title=Role of IRS-2 in insulin and cytokine signalling. |journal=Nature |volume=377 |issue= 6545 |pages= 173–7 |year= 1995 |pmid= 7675087 |doi= 10.1038/377173a0 |bibcode=1995Natur.377..173S |s2cid=4336107 }}
  • {{cite journal |vauthors=Ridderstråle M, Degerman E, Tornqvist H |title=Growth hormone stimulates the tyrosine phosphorylation of the insulin receptor substrate-1 and its association with phosphatidylinositol 3-kinase in primary adipocytes. |journal=J. Biol. Chem. |volume=270 |issue= 8 |pages= 3471–4 |year= 1995 |pmid= 7876077 |doi=10.1074/jbc.270.8.3471 |doi-access=free }}
  • {{cite journal |vauthors=Platanias LC, Uddin S, Yetter A, etal |title=The type I interferon receptor mediates tyrosine phosphorylation of insulin receptor substrate 2. |journal=J. Biol. Chem. |volume=271 |issue= 1 |pages= 278–82 |year= 1996 |pmid= 8550573 |doi=10.1074/jbc.271.1.278 |doi-access=free }}
  • {{cite journal |vauthors=Beitner-Johnson D, Blakesley VA, Shen-Orr Z, etal |title=The proto-oncogene product c-Crk associates with insulin receptor substrate-1 and 4PS. Modulation by insulin growth factor-I (IGF) and enhanced IGF-I signaling. |journal=J. Biol. Chem. |volume=271 |issue= 16 |pages= 9287–90 |year= 1996 |pmid= 8621590 |doi= 10.1074/jbc.271.16.9287|doi-access=free }}
  • {{cite journal |vauthors=Sawka-Verhelle D, Tartare-Deckert S, White MF, Van Obberghen E |title=Insulin receptor substrate-2 binds to the insulin receptor through its phosphotyrosine-binding domain and through a newly identified domain comprising amino acids 591-786. |journal=J. Biol. Chem. |volume=271 |issue= 11 |pages= 5980–3 |year= 1996 |pmid= 8626379 |doi=10.1074/jbc.271.11.5980 |doi-access=free }}
  • {{cite journal |vauthors=He W, Craparo A, Zhu Y, etal |title=Interaction of insulin receptor substrate-2 (IRS-2) with the insulin and insulin-like growth factor I receptors. Evidence for two distinct phosphotyrosine-dependent interaction domains within IRS-2. |journal=J. Biol. Chem. |volume=271 |issue= 20 |pages= 11641–5 |year= 1996 |pmid= 8662806 |doi= 10.1074/jbc.271.20.11641|doi-access=free }}
  • {{cite journal |vauthors=Zhang WR, Li PM, Oswald MA, Goldstein BJ |title=Modulation of insulin signal transduction by eutopic overexpression of the receptor-type protein-tyrosine phosphatase LAR. |journal=Mol. Endocrinol. |volume=10 |issue= 5 |pages= 575–84 |year= 1996 |doi=10.1210/mend.10.5.8732688 |pmid= 8732688 |s2cid=42128485 |doi-access=free }}
  • {{cite journal |vauthors=Argetsinger LS, Norstedt G, Billestrup N, etal |title=Growth hormone, interferon-gamma, and leukemia inhibitory factor utilize insulin receptor substrate-2 in intracellular signaling. |journal=J. Biol. Chem. |volume=271 |issue= 46 |pages= 29415–21 |year= 1997 |pmid= 8910607 |doi=10.1074/jbc.271.46.29415 |doi-access=free }}
  • {{cite journal |vauthors=Thiselton DL, Hampson RM, Nayudu M, etal |title=Mapping the RP2 locus for X-linked retinitis pigmentosa on proximal Xp: a genetically defined 5-cM critical region and exclusion of candidate genes by physical mapping. |journal=Genome Res. |volume=6 |issue= 11 |pages= 1093–102 |year= 1997 |pmid= 8938433 |doi=10.1101/gr.6.11.1093 |doi-access=free }}
  • {{cite journal |vauthors=Izuhara K, Harada N |title=Interleukin-4 activates two distinct pathways of phosphatidylinositol-3 kinase in the same cells. |journal=Biochem. Biophys. Res. Commun. |volume=229 |issue= 2 |pages= 624–9 |year= 1997 |pmid= 8954948 |doi= 10.1006/bbrc.1996.1854 }}
  • {{cite journal |vauthors=Vanhaesebroeck B, Welham MJ, Kotani K, etal |title=P110delta, a novel phosphoinositide 3-kinase in leukocytes. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=94 |issue= 9 |pages= 4330–5 |year= 1997 |pmid= 9113989 |doi=10.1073/pnas.94.9.4330 | pmc=20722 |bibcode=1997PNAS...94.4330V |doi-access=free }}
  • {{cite journal |vauthors=Sawka-Verhelle D, Baron V, Mothe I, etal |title=Tyr624 and Tyr628 in insulin receptor substrate-2 mediate its association with the insulin receptor. |journal=J. Biol. Chem. |volume=272 |issue= 26 |pages= 16414–20 |year= 1997 |pmid= 9195949 |doi=10.1074/jbc.272.26.16414 |doi-access=free }}
  • {{cite journal |vauthors=Algenstaedt P, Antonetti DA, Yaffe MB, Kahn CR |title=Insulin receptor substrate proteins create a link between the tyrosine phosphorylation cascade and the Ca2+-ATPases in muscle and heart. |journal=J. Biol. Chem. |volume=272 |issue= 38 |pages= 23696–702 |year= 1997 |pmid= 9295312 |doi=10.1074/jbc.272.38.23696 |doi-access=free }}

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