Receptor de insulina

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Receptor de insulina
(PDB:3LOH)
Estruturas disponíveis
PDB Busca de ortólogos: PDBe, RCSB
Lista de códigos PDB

1GAG, 1I44, 1IR3, 1IRK, 1P14, 1RQQ, 2AUH, 2B4S, 2DTG, 2HR7, 2Z8C, 3BU3, 3BU5, 3BU6, 3EKK, 3EKN, 3ETA, 3LOH

Identificadores
Símbolos INSR; CD220; HHF5
IDs externos OMIM: 147670 MGI: 96575 HomoloGene: 20090 ChEMBL: 1981 GeneCards: INSR Gene
Número EC 2.7.10.1
Ontologia do gene
Função molecular •protein tyrosine kinase activity
•receptor signaling protein tyrosine kinase activity
•insulin-activated receptor activity
•insulin-like growth factor receptor binding
•protein binding
•ATP binding
•GTP binding
•protein phosphatase binding
•lipoic acid binding
•insulin-like growth factor I binding
•insulin-like growth factor II binding
•protein complex binding
•SH2 domain binding
•3-phosphoinositide-dependent protein kinase binding
•phosphatidylinositol 3-kinase binding
•insulin binding
•insulin receptor substrate binding
•PTB domain binding
Componente celular •nucleus
•cytosol
•plasma membrane
•integral to plasma membrane
•insulin receptor complex
•caveola
•endosome membrane
•membrane
•synapse
Processo biológico •activation of MAPK activity
•negative regulation of protein phosphorylation
•positive regulation of protein phosphorylation
•heart morphogenesis
•carbohydrate metabolic process
•regulation of transcription, DNA-dependent
•G-protein coupled receptor signaling pathway
•positive regulation of cell proliferation
•insulin receptor signaling pathway
•response to glucose stimulus
•response to manganese ion
•regulation of hydrogen peroxide metabolic process
•positive regulation of glycoprotein biosynthetic process
•negative regulation of gene expression
•response to activity
•peptidyl-tyrosine phosphorylation
•transformation of host cell by virus
•signal transduction by phosphorylation
•male sex determination
•positive regulation of cell migration
•exocrine pancreas development
•activation of protein kinase activity
•activation of protein kinase B activity
•response to estradiol stimulus
•negative regulation of transporter activity
•cellular response to insulin stimulus
•response to vitamin D
•response to testosterone stimulus
•response to tumor necrosis factor
•glucose homeostasis
•positive regulation of MAPK cascade
•positive regulation of nitric oxide biosynthetic process
•fat cell differentiation
•response to ethanol
•positive regulation of glycogen biosynthetic process
•positive regulation of DNA replication
•positive regulation of glycolysis
•positive regulation of mitosis
•regulation of embryonic development
•positive regulation of glucose import
•protein autophosphorylation
•positive regulation of developmental growth
•protein heterotetramerization
•response to glucocorticoid stimulus
•positive regulation of protein kinase B signaling cascade
•positive regulation of respiratory burst
•cellular response to growth factor stimulus
Sources: Amigo / QuickGO
Padrões de expressão do ARN
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]
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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

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. PMID 19274663. doi:10.1002/bies.200800210 
  2. ↑ Ebina Y, Ellis L (1985). «The human insulin receptor cDNA: the structural basis for hormone-activated transmembrane signalling.». Cell. 40 (4): 747–58. PMID 2859121. doi:10.1016/0092-8674(85)90334-4 
  3. ↑ Malaguarnera R, Belfiore A (2012). «Proinsulin Binds with High Affinity the Insulin Receptor Isoform A and Predominantly Activates the Mitogenic Pathway.». Endocrinology. Epub. PMID 22355074. doi:10.1210/en.2011-1843 
  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. PMID 19752219. doi:10.1210/er.2008-0047 
  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. ISSN 0012-1797. PMID 10615944. doi:10.2337/diabetes.49.1.13  A referência emprega parâmetros obsoletos |coautor= (ajuda)
  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. ISSN 0006-291X. PMID 8135823. doi:10.1006/bbrc.1994.1297  A referência emprega parâmetros obsoletos |coautor= (ajuda)
  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. ISSN 0021-9258. PMID 7493946. doi:10.1074/jbc.270.49.29189  A referência emprega parâmetros obsoletos |coautor= (ajuda)
  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. ISSN 0950-9232. PMID 10871840. doi:10.1038/sj.onc.1203616  A referência emprega parâmetros obsoletos |coautor= (ajuda)
  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. ISSN 0021-9258. PMID 8621530. doi:10.1074/jbc.271.15.8882  A referência emprega parâmetros obsoletos |coautor= (ajuda)
  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. ISSN 0027-8424. PMC 40781Acessível livremente. PMID 7479769. doi:10.1073/pnas.92.22.10287  A referência emprega parâmetros obsoletos |coautor= (ajuda)
  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. ISSN 0021-9258. PMID 9506989. doi:10.1074/jbc.273.12.6860  A referência emprega parâmetros obsoletos |coautor= (ajuda)
  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. ISSN 0021-9258. PMID 9006901. doi:10.1074/jbc.272.5.2659  A referência emprega parâmetros obsoletos |coautor= (ajuda)
  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. ISSN 0950-9232. PMID 10803466. doi:10.1038/sj.onc.1203469  A referência emprega parâmetros obsoletos |coautor= (ajuda)
  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. ISSN 0888-8809. PMID 11266508. doi:10.1210/me.15.4.565  A referência emprega parâmetros obsoletos |coautor= (ajuda)
  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. ISSN 0012-1797. PMID 12031982. doi:10.2337/diabetes.51.6.1921  A referência emprega parâmetros obsoletos |coautor= (ajuda)
  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. ISSN 0021-9258. PMID 11606564. doi:10.1074/jbc.M101521200  A referência emprega parâmetros obsoletos |coautor= (ajuda)
  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. ISSN 0021-9258. PMID 8626379. doi:10.1074/jbc.271.11.5980  A referência emprega parâmetros obsoletos |coautor= (ajuda)
  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  A referência emprega parâmetros obsoletos |coautor= (ajuda)
  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. ISSN 0938-8990. PMID 10594240. doi:10.1007/s003359901183  A referência emprega parâmetros obsoletos |coautor= (ajuda)
  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. ISSN 0021-9258. PMID 9092546. doi:10.1074/jbc.272.15.10035  A referência emprega parâmetros obsoletos |coautor= (ajuda)

Leitura adicional

  • Pearson RB, Kemp BE (1991). «Protein kinase phosphorylation site sequences and consensus specificity motifs: tabulations». Meth. Enzymol. 200: 62–81. PMID 1956339. doi:10.1016/0076-6879(91)00127-I 
  • Joost HG (1995). «Structural and functional heterogeneity of insulin receptors». Cell. Signal. 7 (2): 85–91. PMID 7794689. doi:10.1016/0898-6568(94)00071-I 
  • O'Dell SD, Day IN (1998). «Insulin-like growth factor II (IGF-II)». Int. J. Biochem. Cell Biol. 30 (7): 767–71. PMID 9722981. doi:10.1016/S1357-2725(98)00048-X 
  • 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. PMID 11075717. doi:10.1507/endocrj.47.373 
  • 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. PMID 12153558. doi:10.1046/j.1432-1033.2002.03038.x