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胰島素樣生長因子1受體

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胰島素樣生長因子1受體
已知的結構
PDB直系同源搜尋: PDBe RCSB
識別號
別名IGF1R;, CD221, IGFIR, IGFR, JTK13, insulin like growth factor 1 receptor, Insulin-like growth factor 1,IGF-1R
外部IDOMIM147370 MGI96433 HomoloGene30997 GeneCardsIGF1R
相關疾病
growth delay due to insulin-like growth factor I resistance[1]
為以下藥物的標靶
色瑞替尼、​AP-26113、​bms-754807、​picropodophyllin[2]
基因位置(人類
15號染色體
染色體15號染色體[3]
15號染色體
胰島素樣生長因子1受體的基因位置
胰島素樣生長因子1受體的基因位置
基因座15q26.3起始98,648,539 bp[3]
終止98,964,530 bp[3]
RNA表達模式


查閱更多表達數據
直系同源
物種人類小鼠
Entrez
Ensembl
UniProt
mRNA​序列

​NM_000875
​NM_001291858
​NM_152452

NM_010513

蛋白序列

NP_000866
​NP_001278787

NP_034643

基因位置​(UCSC)Chr 15: 98.65 – 98.96 MbChr 7: 67.6 – 67.88 Mb
PubMed​查找[5][6]
維基數據
檢視/編輯人類檢視/編輯小鼠

胰島素樣生長因子1受體(英語:insulin-like growth factor 1 receptor,IGF-1R)是人類細胞表面發現的蛋白質,是激素胰島素樣生長因子1(IGF-1)的細胞表面受體,屬於酪氨酸激酶受體家族。其高親和力配體IGF-1,是一種在分子結構上與多肽類激素胰島素類似的激素,在生長發育和成人的合成代謝中有重要作用,可引起骨骼肌或其他組織的過度增殖。此外,IGF-1R對胰島素和IGF-2也有較低的親和力[7]。完全缺失IGF-1受體的小鼠會在生長發育到一定階段時死亡,並伴隨有體重急劇下降,帶有單個IGF-1R等位基因缺失的小鼠仍能正常發育,但存在約15%的體重減少,這表明了此受體強烈的生長促進作用。

結構

IGF-1R的結構

兩個α亞基和兩個β組成了一整個的IGF-1受體。單個α和β亞基都是從一條mRNA前體轉譯而來,轉譯出的蛋白質前體會經歷糖基化蛋白酶解與分子內或分子間的二硫鍵生成,形成由兩條α與兩條β肽鏈形成的跨膜蛋白[8]。如左圖所示,α鏈位於細胞外,通過二硫鍵與β鏈和另一個α鏈連接,β鏈跨過細胞膜,與胞內信號轉導有關。完整的IGF-1R的分子量約有320kDa[7]。這一受體所在的蛋白質家族還包括了胰島素受體胰島素樣生長因子2受體(IGF-2R)以及一些IGF結合蛋白

IGF-1R和胰島素受體有60%的同源性,且胞內都有一個ATP結合位點,參與酪氨酸自我磷酸化。酪氨酸殘基1161、1165和1166及鄰近的自我磷酸化結構被稱為IGF1R的酪氨酸激酶結構域(tyrosine kinase domain)[9]

在於對應配體結合後,α鏈會誘導β的酪氨酸發生自我磷酸化。這一磷酸化事件會觸發下游一系列的信號通路,不同細胞會有所不同,但通常和細胞的生存與增值有關[10][11]

相互作用

胰島素樣生長因子1受體可與下列蛋白質相互作用

調控

已有報道的是IGF1R的表達水平受microRNAmiR-7負調控[28]

相關條目

參考文獻

  1. ^ 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. 
  2. ^ 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. ^ 3.0 3.1 3.2 GRCh38: Ensembl release 89: ENSG00000140443 - Ensembl, May 2017
  4. ^ 4.0 4.1 4.2 GRCm38: Ensembl release 89: ENSMUSG00000005533 - Ensembl, May 2017
  5. ^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine. 
  6. ^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine. 
  7. ^ 7.0 7.1 存档副本. [2018-10-18]. (原始內容存檔於2020-11-30). 
  8. ^ 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. 
  9. ^ 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可免費查閱. PMID 26628682. doi:10.1126/scisignal.aaa6711. 
  10. ^ 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. 
  11. ^ 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. 
  12. ^ Taya S, Inagaki N, Sengiku H, Makino H, Iwamatsu A, Urakawa I, Nagao K, Kataoka S, Kaibuchi K. Direct interaction of insulin-like growth factor-1 receptor with leukemia-associated RhoGEF. J. Cell Biol. November 2001, 155 (5): 809–20. PMC 2150867可免費查閱. PMID 11724822. doi:10.1083/jcb.200106139. 
  13. ^ 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. 
  14. ^ 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. 
  15. ^ 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. 
  16. ^ 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可免費查閱. PMID 12697834. doi:10.1128/mcb.23.9.3363-3372.2003. 
  17. ^ 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. 
  18. ^ 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. 
  19. ^ 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. 
  20. ^ 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可免費查閱. PMID 10082579. 
  21. ^ 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. 
  22. ^ 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. 
  23. ^ 23.0 23.1 Seely BL, Reichart DR, Staubs PA, Jhun BH, Hsu D, Maegawa H, Milarski KL, Saltiel AR, Olefsky JM. 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. 
  24. ^ Santen RJ, Song RX, Zhang Z, Kumar R, Jeng MH, Masamura A, Lawrence J, Berstein L, Yue W. 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. 
  25. ^ 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. 
  26. ^ 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. 
  27. ^ 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. 
  28. ^ Jiang L, Liu X, Chen Z, Jin Y, Heidbreder CE, Kolokythas A, Wang A, Dai Y, Zhou X. 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可免費查閱. PMID 20819078. doi:10.1042/BJ20100859. 

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