Insulinski receptor (IR) je transmembranskireceptor koji aktiviraju insulin, IGF-I, IGF-II, i koji pripada velikoj klasi receptorskih tirozinskih kinaza.[1] U pogledu metabolizma, insulinskih receptor ima ključnu ulogu u regulaciji glukozne homeostaze, funkcionalnog procesa koji pod degenerivnim okolnostima može da dovede do niza kliničkih manifestacija, uključujući dijabetes i kancer.[2][3] Biohemijski, insulinski receptor je kodiran jednim genomINSR, iz koga se alternativnim splajsovanjem tokom transkripcije formiraju bilo IR-A ili IR-B izoforma.[4] Dalje posttranslacione izmene ovih izoformi dovode do formiranja proteolitički skraćenih α i β podjedinica, koje nakon kombinovanja imaju sposobnost formiranja homo ili hetero-dimera, čime nastaje ≈320 kDa disulfidno vezani transmembranski insulinski receptor.[4]
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^Malaguarnera R, Belfiore A (2012). „Proinsulin Binds with High Affinity the Insulin Receptor Isoform A and Predominantly Activates the Mitogenic Pathway.”. Endocrinology. Epub (5): 2152—63. PMID22355074. doi:10.1210/en.2011-1843.
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^Langlais P, Dong LQ, Hu D, Liu F (2000). „Identification of Grb10 as a direct substrate for members of the Src tyrosine kinase family”. Oncogene. 19 (25): 2895—903. PMID10871840. doi:10.1038/sj.onc.1203616.
^Hansen H, Svensson U, Zhu J, Laviola L, Giorgino F, Wolf G, Smith RJ, Riedel H (1996). „Interaction between the Grb10 SH2 domain and the insulin receptor carboxyl terminus”. The Journal of Biological Chemistry. 271 (15): 8882—6. PMID8621530. doi:10.1074/jbc.271.15.8882.
^He W, Rose DW, Olefsky JM, Gustafson TA (1998). „Grb10 interacts differentially with the insulin receptor, insulin-like growth factor I receptor, and epidermal growth factor receptor via the Grb10 Src homology 2 (SH2) domain and a second novel domain located between the pleckstrin homology and SH2 domains”. The Journal of Biological Chemistry. 273 (12): 6860—7. PMID9506989. doi:10.1074/jbc.273.12.6860.
^Frantz JD, Giorgetti-Peraldi S, Ottinger EA, Shoelson SE (1997). „Human GRB-IRbeta/GRB10. Splice variants of an insulin and growth factor receptor-binding protein with PH and SH2 domains”. The Journal of Biological Chemistry. 272 (5): 2659—67. PMID9006901. doi:10.1074/jbc.272.5.2659.
^Kasus-Jacobi A, Béréziat V, Perdereau D, Girard J, Burnol AF (2000). „Evidence for an interaction between the insulin receptor and Grb7. A role for two of its binding domains, PIR and SH2”. Oncogene. 19 (16): 2052—9. PMID10803466. doi:10.1038/sj.onc.1203469.
^Aguirre V, Werner ED, Giraud J, Lee YH, Shoelson SE, White MF (2002). „Phosphorylation of Ser307 in insulin receptor substrate-1 blocks interactions with the insulin receptor and inhibits insulin action”. The Journal of Biological Chemistry. 277 (2): 1531—7. PMID11606564. doi:10.1074/jbc.M101521200.
^Sawka-Verhelle D, Tartare-Deckert S, White MF, Van Obberghen E (1996). „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”. The Journal of Biological Chemistry. 271 (11): 5980—3. PMID8626379. doi:10.1074/jbc.271.11.5980.
^O'Neill TJ, Zhu Y, Gustafson TA (1997). „Interaction of MAD2 with the carboxyl terminus of the insulin receptor but not with the IGFIR. Evidence for release from the insulin receptor after activation”. The Journal of Biological Chemistry. 272 (15): 10035—40. PMID9092546. doi:10.1074/jbc.272.15.10035.
^Braiman L, Alt A, Kuroki T, Ohba M, Bak A, Tennenbaum T, Sampson SR (2001). „Insulin induces specific interaction between insulin receptor and protein kinase C delta in primary cultured skeletal muscle”. Molecular Endocrinology. 15 (4): 565—74. PMID11266508. doi:10.1210/mend.15.4.0612.
^Maegawa H, Ugi S, Adachi M, Hinoda Y, Kikkawa R, Yachi A, Shigeta Y, Kashiwagi A (1994). „Insulin receptor kinase phosphorylates protein tyrosine phosphatase containing Src homology 2 regions and modulates its PTPase activity in vitro”. Biochemical and Biophysical Research Communications. 199 (2): 780—5. PMID8135823. doi:10.1006/bbrc.1994.1297.
^Kharitonenkov A, Schnekenburger J, Chen Z, Knyazev P, Ali S, Zwick E, White M, Ullrich A (1995). „Adapter function of protein-tyrosine phosphatase 1D in insulin receptor/insulin receptor substrate-1 interaction”. The Journal of Biological Chemistry. 270 (49): 29189—93. PMID7493946. doi:10.1074/jbc.270.49.29189.
^Nelms K, O'Neill TJ, Li S, Hubbard SR, Gustafson TA, Paul WE (1999). „Alternative splicing, gene localization, and binding of SH2-B to the insulin receptor kinase domain”. Mammalian Genome. 10 (12): 1160—7. PMID10594240. doi:10.1007/s003359901183.
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