Receptor de insulina

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Receptor de insulina

(PDB:3LOH)

Estruturas disponíveis
PDB Busca de ortólogos: PDBe, RCSB
[Expandir]Lista de códigos PDB

Identificadores

Símbolos INSR; CD220; HHF5

IDs externos OMIM: 147670 MGI: 96575HomoloGene: 20090 ChEMBL: 1981GeneCards: INSR

Gene

Número EC 2.7.10.1

[Expandir]Ontologia do gene

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 NP_000199.2 NP_034698.2

(proteína)

Localização Chr 19: Chr 8:

(UCSC) 7.11 – 7.29 Mb 3.15 – 3.28 Mb

Busca PubMed [1] [2]

 v

 d

 e

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 alternativodurante 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 (Mo
thers 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. ↑ Ir para: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
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
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
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
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
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 40781
. PMID 7479769. doi:10.1073/pnas.92.22.10287
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
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
 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
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
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
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
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
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 1219757 . 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. ISSN 0938-
8990. PMID 10594240. doi:10.1007/s003359901183
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

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. 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