胰岛素样生长因子1受体
胰岛素样生长因子1受体(英語:insulin-like growth factor 1 receptor,IGF-1R)是人类细胞表面发现的蛋白质,是激素胰岛素样生长因子1(IGF-1)的细胞表面受体,属于酪氨酸激酶受体家族。其高亲和力配体IGF-1,是一种在分子结构上与多肽类激素胰岛素类似的激素,在生长发育和成人的合成代谢中有重要作用,可引起骨骼肌或其他组织的过度增殖。此外,IGF-1R对胰岛素和IGF-2也有较低的亲和力[7]。完全缺失IGF-1受体的小鼠会在生长发育到一定阶段时死亡,并伴随有体重急剧下降,带有单个IGF-1R等位基因缺失的小鼠仍能正常发育,但存在约15%的体重减少,这表明了此受体强烈的生长促进作用。
结构 编辑
两个α亚基和两个β组成了一整个的IGF-1受体。单个α和β亚基都是从一条mRNA前体翻译而来,翻译出的蛋白质前体会经历糖基化、蛋白酶解与分子内或分子间的二硫键生成,形成由两条α与两条β肽链形成的跨膜蛋白[8]。如左图所示,α链位于细胞外,通过二硫键与β链和另一个α链连接,β链跨过细胞膜,与胞内的信号转导有关。完整的IGF-1R的分子量约有320kDa[7]。这一受体所在的蛋白质家族还包括了胰岛素受体和胰岛素样生长因子2受体(IGF-2R)以及一些IGF结合蛋白。
IGF-1R和胰岛素受体有60%的同源性,且胞内都有一个ATP结合位点,参与酪氨酸的自我磷酸化。酪氨酸残基1161、1165和1166及邻近的自我磷酸化结构被称为IGF1R的酪氨酸激酶结构域(tyrosine kinase domain)[9]。
在于对应配体结合后,α链会诱导β的酪氨酸发生自我磷酸化。这一磷酸化事件会触发下游一系列的信号通路,不同细胞会有所不同,但通常和细胞的生存与增值有关[10][11]。
相互作用 编辑
胰岛素样生长因子1受体可与下列蛋白质相互作用:
调控 编辑
相关条目 编辑
- 胰岛素受体
- Linsitinib, an inhibitor of IGF-1 in clinical trials for cancer treatment
参考文献 编辑
- ^ 與胰岛素样生长因子1受体相關的疾病;在維基數據上查看/編輯參考.
- ^ 對胰岛素样生长因子1受体起作用的藥物;在維基數據上查看/編輯參考.
- ^ 3.0 3.1 3.2 GRCh38: Ensembl release 89: ENSG00000140443 - Ensembl, May 2017
- ^ 4.0 4.1 4.2 GRCm38: Ensembl release 89: ENSMUSG00000005533 - Ensembl, May 2017
- ^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ 7.0 7.1 存档副本. [2018-10-18]. (原始内容存档于2020-11-30).
- ^ Gregory CW, DeGeorges A, Sikes RA. The IGF axis in the development and progression of prostate cancer. Recent Research Developments in Cancer. 2001: 437–462. ISBN 81-7895-002-2.
- ^ Xu, Q.; Malecka, K. L.; Fink, L.; Jordan, E. J.; Duffy, E.; Kolander, S.; Peterson, J. R.; Dunbrack, R. L. Identifying three-dimensional structures of autophosphorylation complexes in crystals of protein kinases. Science Signaling. 1 December 2015, 8 (405): rs13. PMC 4766099 . PMID 26628682. doi:10.1126/scisignal.aaa6711.
- ^ Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins: biological actions. Endocr. Rev. February 1995, 16 (1): 3–34. PMID 7758431. doi:10.1210/edrv-16-1-3.
- ^ LeRoith D, Werner H, Beitner-Johnson D, Roberts CT. Molecular and cellular aspects of the insulin-like growth factor I receptor. Endocr. Rev. April 1995, 16 (2): 143–63. PMID 7540132. doi:10.1210/edrv-16-2-143.
- ^ Taya, S; Inagaki, N; Sengiku, H; Makino, H; Iwamatsu, A; Urakawa, I; et al. Direct interaction of insulin-like growth factor-1 receptor with leukemia-associated RhoGEF. J. Cell Biol. November 2001, 155 (5): 809–20. PMC 2150867 . PMID 11724822. doi:10.1083/jcb.200106139. 已忽略未知参数
|author-name-separator=
(帮助); 已忽略未知参数|author-separator=
(帮助) - ^ Arbet-Engels, C; Tartare-Deckert, S; Eckhart, W. C-terminal Src kinase associates with ligand-stimulated insulin-like growth factor-I receptor. J. Biol. Chem. February 1999, 274 (9): 5422–8. PMID 10026153. doi:10.1074/jbc.274.9.5422. 已忽略未知参数
|author-separator=
(帮助); 已忽略未知参数|author-name-separator=
(帮助) - ^ 14.0 14.1 14.2 Sehat, B; Andersson, S; Girnita, L; Larsson, O. Identification of c-Cbl as a new ligase for insulin-like growth factor-I receptor with distinct roles from Mdm2 in receptor ubiquitination and endocytosis. Cancer Res. July 2008, 68 (14): 5669–77. PMID 18632619. doi:10.1158/0008-5472.CAN-07-6364. 已忽略未知参数
|author-name-separator=
(帮助); 已忽略未知参数|author-separator=
(帮助) - ^ Rotem-Yehudar, R; Galperin, E; Horowitz, M. Association of insulin-like growth factor 1 receptor with EHD1 and SNAP29. J. Biol. Chem. August 2001, 276 (35): 33054–60. PMID 11423532. doi:10.1074/jbc.M009913200. 已忽略未知参数
|author-separator=
(帮助); 已忽略未知参数|author-name-separator=
(帮助) - ^ 16.0 16.1 Vecchione, A; Marchese, A; Henry, P; Rotin, D; Morrione, A. The Grb10/Nedd4 complex regulates ligand-induced ubiquitination and stability of the insulin-like growth factor I receptor. Mol. Cell. Biol. May 2003, 23 (9): 3363–72. PMC 153198 . PMID 12697834. doi:10.1128/mcb.23.9.3363-3372.2003. 已忽略未知参数
|author-name-separator=
(帮助); 已忽略未知参数|author-separator=
(帮助) - ^ 17.0 17.1 17.2 Dey, BR; Frick, K; Lopaczynski, W; Nissley, SP; Furlanetto, RW. Evidence for the direct interaction of the insulin-like growth factor I receptor with IRS-1, Shc, and Grb10. Mol. Endocrinol. June 1996, 10 (6): 631–41. PMID 8776723. doi:10.1210/mend.10.6.8776723. 已忽略未知参数
|author-name-separator=
(帮助); 已忽略未知参数|author-separator=
(帮助) - ^ He, W; Rose, DW; Olefsky, JM; Gustafson, TA. 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. March 1998, 273 (12): 6860–7. PMID 9506989. doi:10.1074/jbc.273.12.6860. 已忽略未知参数
|author-name-separator=
(帮助); 已忽略未知参数|author-separator=
(帮助) - ^ Morrione, A; Valentinis, B; Li, S; Ooi, JY; Margolis, B; Baserga, R. Grb10: A new substrate of the insulin-like growth factor I receptor. Cancer Res. July 1996, 56 (14): 3165–7. PMID 8764099. 已忽略未知参数
|author-name-separator=
(帮助); 已忽略未知参数|author-separator=
(帮助) - ^ 20.0 20.1 Mañes, S; Mira, E; Gómez-Mouton, C; Zhao, ZJ; Lacalle, RA; Martínez-A, C. Concerted activity of tyrosine phosphatase SHP-2 and focal adhesion kinase in regulation of cell motility. Mol. Cell. Biol. April 1999, 19 (4): 3125–35. PMC 84106 . PMID 10082579. 已忽略未知参数
|author-name-separator=
(帮助); 已忽略未知参数|author-separator=
(帮助) - ^ 21.0 21.1 Tartare-Deckert, S; Sawka-Verhelle, D; Murdaca, J; Van Obberghen, E. Evidence for a differential interaction of SHC and the insulin receptor substrate-1 (IRS-1) with the insulin-like growth factor-I (IGF-I) receptor in the yeast two-hybrid system. J. Biol. Chem. October 1995, 270 (40): 23456–60. PMID 7559507. doi:10.1074/jbc.270.40.23456. 已忽略未知参数
|author-name-separator=
(帮助); 已忽略未知参数|author-separator=
(帮助) - ^ Mothe, I; Delahaye, L; Filloux, C; Pons, S; White, MF; Van Obberghen, E. Interaction of wild type and dominant-negative p55PIK regulatory subunit of phosphatidylinositol 3-kinase with insulin-like growth factor-1 signaling proteins. Mol. Endocrinol. December 1997, 11 (13): 1911–23. PMID 9415396. doi:10.1210/mend.11.13.0029. 已忽略未知参数
|author-name-separator=
(帮助); 已忽略未知参数|author-separator=
(帮助) - ^ 23.0 23.1 Seely, BL; Reichart, DR; Staubs, PA; Jhun, BH; Hsu, D; Maegawa, H; et al. Localization of the insulin-like growth factor I receptor binding sites for the SH2 domain proteins p85, Syp, and GTPase activating protein. J. Biol. Chem. August 1995, 270 (32): 19151–7. PMID 7642582. doi:10.1074/jbc.270.32.19151. 已忽略未知参数
|author-name-separator=
(帮助); 已忽略未知参数|author-separator=
(帮助) - ^ Santen, RJ; Song, RX; Zhang, Z; Kumar, R; Jeng, MH; Masamura, A; et al. Long-term estradiol deprivation in breast cancer cells up-regulates growth factor signaling and enhances estrogen sensitivity. Endocr. Relat. Cancer. 12. July 2005,. 12 Suppl 1: S61–73. PMID 16113100. doi:10.1677/erc.1.01018. 已忽略未知参数
|author-name-separator=
(帮助); 已忽略未知参数|author-separator=
(帮助) - ^ Dey, BR; Spence, SL; Nissley, P; Furlanetto, RW. Interaction of human suppressor of cytokine signaling (SOCS)-2 with the insulin-like growth factor-I receptor. J. Biol. Chem. September 1998, 273 (37): 24095–101. PMID 9727029. doi:10.1074/jbc.273.37.24095. 已忽略未知参数
|author-name-separator=
(帮助); 已忽略未知参数|author-separator=
(帮助) - ^ Dey, BR; Furlanetto, RW; Nissley, P. Suppressor of cytokine signaling (SOCS)-3 protein interacts with the insulin-like growth factor-I receptor. Biochem. Biophys. Res. Commun. November 2000, 278 (1): 38–43. PMID 11071852. doi:10.1006/bbrc.2000.3762. 已忽略未知参数
|author-separator=
(帮助); 已忽略未知参数|author-name-separator=
(帮助) - ^ Craparo, A; Freund, R; Gustafson, TA. 14-3-3 (epsilon) interacts with the insulin-like growth factor I receptor and insulin receptor substrate I in a phosphoserine-dependent manner. J. Biol. Chem. April 1997, 272 (17): 11663–9. PMID 9111084. doi:10.1074/jbc.272.17.11663. 已忽略未知参数
|author-separator=
(帮助); 已忽略未知参数|author-name-separator=
(帮助) - ^ Jiang, L; Liu, X; Chen, Z; Jin, Y; Heidbreder, CE; Kolokythas, A; et al. MicroRNA-7 targets IGF1R (insulin-like growth factor 1 receptor) in tongue squamous cell carcinoma cells. Biochemical Journal. 2010, 432 (1): 199–205. PMC 3130335 . PMID 20819078. doi:10.1042/BJ20100859. 已忽略未知参数
|author-name-separator=
(帮助); 已忽略未知参数|author-separator=
(帮助)
延伸阅读 编辑
- Benito, M; Valverde, AM; Lorenzo, M. IGF-I: a mitogen also involved in differentiation processes in mammalian cells.. Int. J. Biochem. Cell Biol. 1996, 28 (5): 499–510. PMID 8697095. doi:10.1016/1357-2725(95)00168-9. 已忽略未知参数
|author-separator=
(帮助); 已忽略未知参数|author-name-separator=
(帮助) - Butler, AA; Yakar, S; Gewolb, IH; Karas, M; Okubo, Y; LeRoith, D. Insulin-like growth factor-I receptor signal transduction: at the interface between physiology and cell biology. Comp. Biochem. Physiol. B, Biochem. Mol. Biol. 1999, 121 (1): 19–26. PMID 9972281. doi:10.1016/S0305-0491(98)10106-2. 已忽略未知参数
|author-name-separator=
(帮助); 已忽略未知参数|author-separator=
(帮助) - Zhang, X; Yee, D. Tyrosine kinase signalling in breast cancer: insulin-like growth factors and their receptors in breast cancer.. Breast Cancer Res. 2001, 2 (3): 170–5. PMC 138771 . PMID 11250706. doi:10.1186/bcr50. 已忽略未知参数
|author-separator=
(帮助); 已忽略未知参数|author-name-separator=
(帮助) - Gross, JM; Yee, D. The type-1 insulin-like growth factor receptor tyrosine kinase and breast cancer: biology and therapeutic relevance.. Cancer Metastasis Rev. 2004, 22 (4): 327–36. PMID 12884909. doi:10.1023/A:1023720928680. 已忽略未知参数
|author-separator=
(帮助); 已忽略未知参数|author-name-separator=
(帮助) - Adams, TE; McKern, NM; Ward, CW. Signalling by the type 1 insulin-like growth factor receptor: interplay with the epidermal growth factor receptor.. Growth Factors. 2005, 22 (2): 89–95. PMID 15253384. doi:10.1080/08977190410001700998. 已忽略未知参数
|author-separator=
(帮助); 已忽略未知参数|author-name-separator=
(帮助) - Surmacz, E; Bartucci, M. Role of estrogen receptor alpha in modulating IGF-I receptor signaling and function in breast cancer.. J. Exp. Clin. Cancer Res. 2005, 23 (3): 385–94. PMID 15595626. 已忽略未知参数
|author-separator=
(帮助); 已忽略未知参数|author-name-separator=
(帮助) - Wood, AW; Duan, C; Bern, HA. Insulin-like growth factor signaling in fish. Int. Rev. Cytol. International Review of Cytology. 2005, 243: 215–85. ISBN 9780123646477. PMID 15797461. doi:10.1016/S0074-7696(05)43004-1. 已忽略未知参数
|author-name-separator=
(帮助); 已忽略未知参数|author-separator=
(帮助) - Sarfstein, R; Maor, S; Reizner, N; Abramovitch, S; Werner, H. Transcriptional regulation of the insulin-like growth factor-I receptor gene in breast cancer. Mol. Cell. Endocrinol. 2006, 252 (1–2): 241–6. PMID 16647191. doi:10.1016/j.mce.2006.03.018. 已忽略未知参数
|author-name-separator=
(帮助); 已忽略未知参数|author-separator=
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