Receptor de insulina

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Receptor de insulina
(PDB:3LOH)
Estruturas disponíveis
PDB Busca de ortólogos: PDBe, RCSB
Identificadores
Símbolos INSR; CD220; HHF5
IDs externos OMIM: 147670 MGI96575 HomoloGene20090 ChEMBL: 1981 GeneCards: INSR Gene
Número EC 2.7.10.1
Padrões de expressão do ARN
PBB GE INSR 213792 s at tn.png
Mais dados de expressão
Ortólogos
Espécies Humano Rato
Entrez 3643 16337
Ensembl ENSG00000171105 ENSMUSG00000005534
UniProt P06213 P15208
RefSeq (mRNA) NM_000208.2 NM_010568.2
RefSeq (proteína) NP_000199.2 NP_034698.2
Localização (UCSC) Chr 19:
7.11 – 7.29 Mb
Chr 8:
3.15 – 3.28 Mb
Busca PubMed [1] [2]

O receptor de insulina é um receptor transmembranar que é activado pela insulina, IGF-I, IGF-II, pertencendo à grande classe dos receptores tirosina quinase.[1]

Do ponto de vista metabólico, o receptor de insulina desempenha um papel central na regulação da homeostase da glucose, um processo funcional que quando em condições degeneradas podem resultar numa variedade de manifestações clínicas como a diabetes e o cancro.[2][3]

Bioquimicamente, o receptor de insulina é codificado por um único gene, INSR, a partir do qual e por splicing alternativo durante a transcrição, resulta nas isoformas IR-A ou IR-B.[4]

Eventos pós-translacionais a jusante, afectando cada uma das isoformas, resulta na formação através de clivagem proteolítica, de subunidades alfa e beta, que após combinação são capazes de homo- ou heterodimerização com vista à produção do receptor transmembranar de insulina.[4]

Interacções[editar | editar código-fonte]

Mostrou-se que o receptor de insulina interage com ectonucleótido pirofosfatase/fosfodiesterase 1,[5] PTPN11,[6][7] GRB10,[8][9][10][11][12] GRB7,[13] PRKCD,[14][15] IRS1,[16][17] SH2B1[18][19] e SMAD2 (Mothers against decapentaplegic homolog 2).[20]

Referências

  1. Ward CW, Lawrence MC (2009). «Ligand-induced activation of the insulin receptor: a multi-step process involving structural changes in both the ligand and the receptor». BioEssays. 31 (4): 422–34. doi:10.1002/bies.200800210. PMID 19274663 
  2. Ebina Y, Ellis L (1985). «The human insulin receptor cDNA: the structural basis for hormone-activated transmembrane signalling.». Cell. 40 (4): 747–58. doi:10.1016/0092-8674(85)90334-4. PMID 2859121 
  3. Malaguarnera R, Belfiore A (2012). «Proinsulin Binds with High Affinity the Insulin Receptor Isoform A and Predominantly Activates the Mitogenic Pathway.». Endocrinology. Epub. doi:10.1210/en.2011-1843. PMID 22355074 
  4. a b Belfiore A, Frasca F (2009). «Insulin receptor isoforms and insulin receptor/insulin-like growth factor receptor hybrids in physiology and disease.». Endocr Rev. 30 (6): 586–623. doi:10.1210/er.2008-0047. PMID 19752219 
  5. Maddux, B A; Goldfine I D (2000). «Membrane glycoprotein PC-1 inhibition of insulin receptor function occurs via direct interaction with the receptor alpha-subunit». UNITED STATES. Diabetes. 49 (1): 13–9. doi:10.2337/diabetes.49.1.13. ISSN 0012-1797. PMID 10615944 
  6. 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». UNITED STATES. Biochem. Biophys. Res. Commun. 199 (2): 780–5. doi:10.1006/bbrc.1994.1297. ISSN 0006-291X. PMID 8135823 
  7. 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». UNITED STATES. J. Biol. Chem. 270 (49): 29189–93. doi:10.1074/jbc.270.49.29189. ISSN 0021-9258. PMID 7493946 
  8. Langlais, P; Dong L Q, Hu D, Liu F (2000). «Identification of Grb10 as a direct substrate for members of the Src tyrosine kinase family». ENGLAND. Oncogene. 19 (25): 2895–903. doi:10.1038/sj.onc.1203616. ISSN 0950-9232. PMID 10871840 
  9. Hansen, H; Svensson U, Zhu J, Laviola L, Giorgino F, Wolf G, Smith R J, Riedel H (1996). «Interaction between the Grb10 SH2 domain and the insulin receptor carboxyl terminus». UNITED STATES. J. Biol. Chem. 271 (15): 8882–6. doi:10.1074/jbc.271.15.8882. ISSN 0021-9258. PMID 8621530 
  10. Liu, F; Roth R A (1995). «Grb-IR: a SH2-domain-containing protein that binds to the insulin receptor and inhibits its function». UNITED STATES. Proc. Natl. Acad. Sci. U.S.A. 92 (22): 10287–91. Bibcode:1995PNAS...9210287L. doi:10.1073/pnas.92.22.10287. ISSN 0027-8424. PMC 40781Acessível livremente. PMID 7479769 
  11. He, W; Rose D W, Olefsky J M, Gustafson T A (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». UNITED STATES. J. Biol. Chem. 273 (12): 6860–7. doi:10.1074/jbc.273.12.6860. ISSN 0021-9258. PMID 9506989 
  12. Frantz, J D; Giorgetti-Peraldi S, Ottinger E A, Shoelson S E (1997). «Human GRB-IRbeta/GRB10. Splice variants of an insulin and growth factor receptor-binding protein with PH and SH2 domains». UNITED STATES. J. Biol. Chem. 272 (5): 2659–67. doi:10.1074/jbc.272.5.2659. ISSN 0021-9258. PMID 9006901 
  13. Kasus-Jacobi, A; Béréziat V, Perdereau D, Girard J, Burnol A F (2000). «Evidence for an interaction between the insulin receptor and Grb7. A role for two of its binding domains, PIR and SH2». ENGLAND. Oncogene. 19 (16): 2052–9. doi:10.1038/sj.onc.1203469. ISSN 0950-9232. PMID 10803466 
  14. Braiman, L; Alt A, Kuroki T, Ohba M, Bak A, Tennenbaum T, Sampson S R (2001). «Insulin induces specific interaction between insulin receptor and protein kinase C delta in primary cultured skeletal muscle». United States. Mol. Endocrinol. 15 (4): 565–74. doi:10.1210/me.15.4.565. ISSN 0888-8809. PMID 11266508 
  15. Rosenzweig, Tovit; Braiman Liora, Bak Asia, Alt Addy, Kuroki Toshio, Sampson Sanford R (2002). «Differential effects of tumor necrosis factor-alpha on protein kinase C isoforms alpha and delta mediate inhibition of insulin receptor signaling». United States. Diabetes. 51 (6): 1921–30. doi:10.2337/diabetes.51.6.1921. ISSN 0012-1797. PMID 12031982 
  16. Aguirre, Vincent; Werner Eric D, Giraud Jodel, Lee Yong Hee, Shoelson Steve E, White Morris F (2002). «Phosphorylation of Ser307 in insulin receptor substrate-1 blocks interactions with the insulin receptor and inhibits insulin action». United States. J. Biol. Chem. 277 (2): 1531–7. doi:10.1074/jbc.M101521200. ISSN 0021-9258. PMID 11606564 
  17. Sawka-Verhelle, D; Tartare-Deckert S, White M F, 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». UNITED STATES. J. Biol. Chem. 271 (11): 5980–3. doi:10.1074/jbc.271.11.5980. ISSN 0021-9258. PMID 8626379 
  18. Kotani, K; Wilden P, Pillay T S (1998). «SH2-Balpha is an insulin-receptor adapter protein and substrate that interacts with the activation loop of the insulin-receptor kinase». ENGLAND. Biochem. J. 335 (1): 103–9. ISSN 0264-6021. PMC 1219757Acessível livremente. PMID 9742218 
  19. Nelms, K; O'Neill T J, Li S, Hubbard S R, Gustafson T A, Paul W E (1999). «Alternative splicing, gene localization, and binding of SH2-B to the insulin receptor kinase domain». UNITED STATES. Mamm. Genome. 10 (12): 1160–7. doi:10.1007/s003359901183. ISSN 0938-8990. PMID 10594240 
  20. O'Neill, T J; Zhu Y, Gustafson T A (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». UNITED STATES. J. Biol. Chem. 272 (15): 10035–40. doi:10.1074/jbc.272.15.10035. ISSN 0021-9258. PMID 9092546 

Leitura adicional[editar | editar código-fonte]

  • Pearson RB, Kemp BE (1991). «Protein kinase phosphorylation site sequences and consensus specificity motifs: tabulations». Meth. Enzymol. 200: 62–81. doi:10.1016/0076-6879(91)00127-I. PMID 1956339 
  • Joost HG (1995). «Structural and functional heterogeneity of insulin receptors». Cell. Signal. 7 (2): 85–91. doi:10.1016/0898-6568(94)00071-I. PMID 7794689 
  • O'Dell SD, Day IN (1998). «Insulin-like growth factor II (IGF-II)». Int. J. Biochem. Cell Biol. 30 (7): 767–71. doi:10.1016/S1357-2725(98)00048-X. PMID 9722981 
  • Lopaczynski W (1999). «Differential regulation of signaling pathways for insulin and insulin-like growth factor I». Acta Biochim. Pol. 46 (1): 51–60. PMID 10453981 
  • Sasaoka T, Kobayashi M (2000). «The functional significance of Shc in insulin signaling as a substrate of the insulin receptor». Endocr. J. 47 (4): 373–81. doi:10.1507/endocrj.47.373. PMID 11075717 
  • Perz M, Torlińska T (2001). «Insulin receptor—structural and functional characteristics». Med. Sci. Monit. 7 (1): 169–77. PMID 11208515 
  • Benaim G, Villalobo A (2002). «Phosphorylation of calmodulin. Functional implications». Eur. J. Biochem. 269 (15): 3619–31. doi:10.1046/j.1432-1033.2002.03038.x. PMID 12153558