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]
↑Ward CW, Lawrence MC (April 2009). „Ligand-induced activation of the insulin receptor: a multi-step process involving structural changes in both the ligand and the receptor”. BioEssays31 (4): 422–34. DOI:10.1002/bies.200800210. PMID19274663.
↑Ebina Y, Ellis L (April 1985). „The human insulin receptor cDNA: the structural basis for hormone-activated transmembrane signalling.”. Cell40 (4): 747–58. DOI:10.1016/0092-8674(85)90334-4. PMID2859121.
↑Malaguarnera R, Belfiore A (February 2012). „Proinsulin Binds with High Affinity the Insulin Receptor Isoform A and Predominantly Activates the Mitogenic Pathway.”. Endocrinology.Epub (5): 2152–63. DOI:10.1210/en.2011-1843. PMID22355074.
↑ 4,04,1Belfiore A, Frasca F (Oct 2009). „Insulin receptor isoforms and insulin receptor/insulin-like growth factor receptor hybrids in physiology and disease.”. Endocr Rev30 (6): 586–623. DOI:10.1210/er.2008-0047. PMID19752219.
↑Maegawa, H; Ugi S; Adachi M; Hinoda Y; Kikkawa R; Yachi A; Shigeta Y; Kashiwagi A (Mar 1994). „Insulin receptor kinase phosphorylates protein tyrosine phosphatase containing Src homology 2 regions and modulates its PTPase activity in vitro”. Biochem. Biophys. Res. Commun. (UNITED STATES) 199 (2): 780–5. DOI:10.1006/bbrc.1994.1297. ISSN0006-291X. PMID8135823.
↑Kharitonenkov, A; Schnekenburger J; Chen Z; Knyazev P; Ali S; Zwick E; White M; Ullrich A (Dec 1995). „Adapter function of protein-tyrosine phosphatase 1D in insulin receptor/insulin receptor substrate-1 interaction”. J. Biol. Chem. (UNITED STATES) 270 (49): 29189–93. DOI:10.1074/jbc.270.49.29189. ISSN0021-9258. PMID7493946.
↑Langlais, P; Dong L Q; Hu D; Liu F (Jun 2000). „Identification of Grb10 as a direct substrate for members of the Src tyrosine kinase family”. Oncogene (ENGLAND) 19 (25): 2895–903. DOI:10.1038/sj.onc.1203616. ISSN0950-9232. PMID10871840.
↑Hansen, H; Svensson U; Zhu J; Laviola L; Giorgino F; Wolf G; Smith R J; Riedel H (Apr 1996). „Interaction between the Grb10 SH2 domain and the insulin receptor carboxyl terminus”. J. Biol. Chem. (UNITED STATES) 271 (15): 8882–6. DOI:10.1074/jbc.271.15.8882. ISSN0021-9258. PMID8621530.
↑He, W; Rose D W; Olefsky J M; Gustafson T A (Mar 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”. J. Biol. Chem. (UNITED STATES) 273 (12): 6860–7. DOI:10.1074/jbc.273.12.6860. ISSN0021-9258. PMID9506989.
↑Frantz, J D; Giorgetti-Peraldi S; Ottinger E A; Shoelson S E (Jan 1997). „Human GRB-IRbeta/GRB10. Splice variants of an insulin and growth factor receptor-binding protein with PH and SH2 domains”. J. Biol. Chem. (UNITED STATES) 272 (5): 2659–67. DOI:10.1074/jbc.272.5.2659. ISSN0021-9258. PMID9006901.
↑Kasus-Jacobi, A; Béréziat V; Perdereau D; Girard J; Burnol A F (Apr 2000). „Evidence for an interaction between the insulin receptor and Grb7. A role for two of its binding domains, PIR and SH2”. Oncogene (ENGLAND) 19 (16): 2052–9. DOI:10.1038/sj.onc.1203469. ISSN0950-9232. PMID10803466.
↑Braiman, L; Alt A; Kuroki T; Ohba M; Bak A; Tennenbaum T; Sampson S R (Apr 2001). „Insulin induces specific interaction between insulin receptor and protein kinase C delta in primary cultured skeletal muscle”. Mol. Endocrinol. (United States) 15 (4): 565–74. DOI:10.1210/mend.15.4.0612. ISSN0888-8809. PMID11266508.
↑Aguirre, Vincent; Werner Eric D; Giraud Jodel; Lee Yong Hee; Shoelson Steve E; White Morris F (Jan 2002). „Phosphorylation of Ser307 in insulin receptor substrate-1 blocks interactions with the insulin receptor and inhibits insulin action”. J. Biol. Chem. (United States) 277 (2): 1531–7. DOI:10.1074/jbc.M101521200. ISSN0021-9258. PMID11606564.
↑Sawka-Verhelle, D; Tartare-Deckert S, White M F, Van Obberghen E (Mar 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”. J. Biol. Chem. (UNITED STATES) 271 (11): 5980–3. DOI:10.1074/jbc.271.11.5980. ISSN0021-9258. PMID8626379.
↑Nelms, K; O'Neill T J; Li S; Hubbard S R; Gustafson T A; Paul W E (Dec 1999). „Alternative splicing, gene localization, and binding of SH2-B to the insulin receptor kinase domain”. Mamm. Genome (UNITED STATES) 10 (12): 1160–7. DOI:10.1007/s003359901183. ISSN0938-8990. PMID10594240.
↑O'Neill, T J; Zhu Y; Gustafson T A (Apr 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”. J. Biol. Chem. (UNITED STATES) 272 (15): 10035–40. DOI:10.1074/jbc.272.15.10035. ISSN0021-9258. PMID9092546.
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