IRS4 explained

Insulin receptor substrate 4 is a protein that in humans is encoded by the IRS4 gene.^{[1] [2] [3]}

IRS4 encodes the insulin receptor substrate 4, a cytoplasmic protein that contains many potential tyrosine and serine/threonine phosphorylation sites. Tyrosine-phosphorylated IRS4 protein has been shown to associate with cytoplasmic signalling molecules that contain SH2 domains. The IRS4 protein is phosphorylated by the insulin receptor tyrosine kinase upon receptor stimulation.^[3]

Interactions

IRS4 has been shown to interact with CRK^{[4] [5]} and NISCH.^[6]

Further reading

• White MF . The IRS-signalling system: a network of docking proteins that mediate insulin action. . Mol. Cell. Biochem. . 182 . 1–2 . 3–11 . 1999 . 9609109 . 10.1023/A:1006806722619 . 32623861 .
• Koval AP, Karas M, Zick Y, LeRoith D . Interplay of the proto-oncogene proteins CrkL and CrkII in insulin-like growth factor-I receptor-mediated signal transduction. . J. Biol. Chem. . 273 . 24 . 14780–7 . 1998 . 9614078 . 10.1074/jbc.273.24.14780 . free .
• Uchida T, Myers MG, White MF . IRS-4 mediates protein kinase B signaling during insulin stimulation without promoting antiapoptosis. . Mol. Cell. Biol. . 20 . 1 . 126–38 . 2000 . 10594015 . 10.1128/MCB.20.1.126-138.2000 . 85068 .
• Karas M, Koval AP, Zick Y, LeRoith D . The insulin-like growth factor I receptor-induced interaction of insulin receptor substrate-4 and Crk-II. . Endocrinology . 142 . 5 . 1835–40 . 2001 . 11316748 . 10.1210/en.142.5.1835 . free .
• Sano H, Liu SC, Lane WS, etal . Insulin receptor substrate 4 associates with the protein IRAS. . J. Biol. Chem. . 277 . 22 . 19439–47 . 2002 . 11912194 . 10.1074/jbc.M111838200 . free .
• Krebs DL, Uren RT, Metcalf D, etal . SOCS-6 binds to insulin receptor substrate 4, and mice lacking the SOCS-6 gene exhibit mild growth retardation. . Mol. Cell. Biol. . 22 . 13 . 4567–78 . 2002 . 12052866 . 10.1128/MCB.22.13.4567-4578.2002 . 133908 .
• Schreyer S, Ledwig D, Rakatzi I, etal . Insulin receptor substrate-4 is expressed in muscle tissue without acting as a substrate for the insulin receptor. . Endocrinology . 144 . 4 . 1211–8 . 2003 . 12639902 . 10.1210/en.2002-220723 . free .
• Escribano O, Fernández-Moreno MD, Zueco JA, etal . Insulin receptor substrate-4 signaling in quiescent rat hepatocytes and in regenerating rat liver. . Hepatology . 37 . 6 . 1461–9 . 2003 . 12774026 . 10.1053/jhep.2003.50245 . 20484894 . free .
• Yen HW, Jakimiuk AJ, Munir I, Magoffin DA . Selective alterations in insulin receptor substrates-1, -2 and -4 in theca but not granulosa cells from polycystic ovaries. . Mol. Hum. Reprod. . 10 . 7 . 473–9 . 2005 . 15155816 . 10.1093/molehr/gah066 . free .
• Hinsby AM, Olsen JV, Mann M . Tyrosine phosphoproteomics of fibroblast growth factor signaling: a role for insulin receptor substrate-4. . J. Biol. Chem. . 279 . 45 . 46438–47 . 2004 . 15316024 . 10.1074/jbc.M404537200 . free .
• Jin J, Smith FD, Stark C, etal . Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization. . Curr. Biol. . 14 . 16 . 1436–50 . 2004 . 15324660 . 10.1016/j.cub.2004.07.051 . 2371325 . free . 2004CBio...14.1436J .
• Mihindukulasuriya KA, Zhou G, Qin J, Tan TH . Protein phosphatase 4 interacts with and down-regulates insulin receptor substrate 4 following tumor necrosis factor-alpha stimulation. . J. Biol. Chem. . 279 . 45 . 46588–94 . 2004 . 15331607 . 10.1074/jbc.M408067200 . free .
• Qiu H, Zappacosta F, Su W, etal . Interaction between Brk kinase and insulin receptor substrate-4. . Oncogene . 24 . 36 . 5656–64 . 2005 . 15870689 . 10.1038/sj.onc.1208721 . free .
• Cuevas EP, Escribano O, Chiloeches A, etal . Role of insulin receptor substrate-4 in IGF-I-stimulated HEPG2 proliferation. . J. Hepatol. . 46 . 6 . 1089–98 . 2007 . 17408801 . 10.1016/j.jhep.2007.01.031 .

Notes and References

1. Lavan BE, Fantin VR, Chang ET, Lane WS, Keller SR, Lienhard GE . A novel 160-kDa phosphotyrosine protein in insulin-treated embryonic kidney cells is a new member of the insulin receptor substrate family . J Biol Chem . 272 . 34 . 21403–7 . Sep 1997 . 9261155 . 10.1074/jbc.272.34.21403 . free .
2. Fantin VR, Sparling JD, Slot JW, Keller SR, Lienhard GE, Lavan BE . Characterization of insulin receptor substrate 4 in human embryonic kidney 293 cells . J Biol Chem . 273 . 17 . 10726–32 . May 1998 . 9553137 . 10.1074/jbc.273.17.10726 . free .
3. Web site: Entrez Gene: IRS4 insulin receptor substrate 4.
4. Karas . M . Koval A P . Zick Y . LeRoith D . May 2001 . The insulin-like growth factor I receptor-induced interaction of insulin receptor substrate-4 and Crk-II . . 142 . 5 . 1835–40 . United States. 0013-7227. 11316748 . 10.1210/endo.142.5.8135 . free .
5. Koval . A P . Karas M . Zick Y . LeRoith D . Jun 1998 . Interplay of the proto-oncogene proteins CrkL and CrkII in insulin-like growth factor-I receptor-mediated signal transduction . J. Biol. Chem. . 273 . 24 . 14780–7 . UNITED STATES. 0021-9258. 9614078 . 10.1074/jbc.273.24.14780 . free .
6. Sano . Hiroyuki . Liu Simon C H . Lane William S . Piletz John E . Lienhard Gustav E . May 2002 . Insulin receptor substrate 4 associates with the protein IRAS . J. Biol. Chem. . 277 . 22 . 19439–47 . United States. 0021-9258. 11912194 . 10.1074/jbc.M111838200 . free .