胰岛素样生长因子1受体

胰岛素样生长因子1受体
已知的結構
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	1IGR、1JQH、1K3A、1M7N、1P4O、2OJ9、2ZM3、3D94、3F5P、3I81、3LVP、3LW0、3NW5、3NW6、3NW7、3O23、3QQU、4D2R、4XSS、5HZN
識別號
别名	IGF1R；, CD221, IGFIR, IGFR, JTK13, insulin like growth factor 1 receptor, Insulin-like growth factor 1，IGF-1R
外部ID	OMIM：147370 MGI：96433 HomoloGene：30997 GeneCards：IGF1R
相關疾病
	growth delay due to insulin-like growth factor I resistance
為以下藥物的標靶
	色瑞替尼、AP-26113、bms-754807、picropodophyllin
基因位置（人类）
染色体	15號染色體
终止	98,964,530 bp
基因位置（小鼠）
染色体	小鼠7号染色体
终止	67,883,416 bp
RNA表达模式
	; ;
	查阅更多表达数据
基因本體
分子功能	• 轉移酶活性; • 核苷酸結合; • 蛋白激酶活性; • insulin-like growth factor binding; • insulin receptor binding; • insulin binding; • 激酶活性; • phosphatidylinositol 3-kinase binding; • insulin-like growth factor-activated receptor activity; • 血浆蛋白结合; • 相同蛋白质结合; • transmembrane receptor protein tyrosine kinase activity; • insulin receptor substrate binding; • protein tyrosine kinase activity; • ATP結合; • insulin-like growth factor I binding; • insulin-activated receptor activity;
細胞組分	• integral component of membrane; • 膜; • 細胞內膜結合細胞器; • receptor complex; • 细胞膜; • integral component of plasma membrane; • alphav-beta3 integrin-IGF-1-IGF1R complex; • insulin receptor complex; • 轴突;
生物學過程	• insulin receptor signaling pathway; • insulin-like growth factor receptor signaling pathway; • 磷酸化; • transmembrane receptor protein tyrosine kinase signaling pathway; • positive regulation of cell migration; • negative regulation of apoptotic process; • protein tetramerization; • positive regulation of DNA replication; • protein phosphorylation; • regulation of JNK cascade; • 免疫反应; • positive regulation of cell population proliferation; • peptidyl-tyrosine autophosphorylation; • 自體磷酸化; • phosphatidylinositol 3-kinase signaling; • phosphatidylinositol-mediated signaling; • 訊息傳遞; • positive regulation of phosphatidylinositol 3-kinase signaling; • glucose homeostasis; • positive regulation of protein-containing complex disassembly; • positive regulation of MAPK cascade; • anatomical structure development; • positive regulation of protein kinase B signaling; • cellular response to glucose stimulus; • dendritic spine maintenance; • amyloid-beta clearance; • positive regulation of cold-induced thermogenesis; • cellular response to amyloid-beta;
	Sources:Amigo / QuickGO
直系同源
	3480
	16001
	ENSG00000140443
	ENSMUSG00000005533
	P08069
	Q60751
	NM_000875; NM_001291858; NM_152452
	NM_010513
	NP_000866; NP_001278787
	NP_034643
	維基數據
檢視/編輯人類	檢視/編輯小鼠

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

IGF-1R的结构

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

胰岛素样生长因子1受体可与下列蛋白质相互作用：

调控

已有报道的是IGF1R的表达水平受microRNA miR-7负调控^[28]。

参考文献

^ 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, 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  . PMID 11724822. doi:10.1083/jcb.200106139.
^ 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.
^ ^14.0 ^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.
^ 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.
^ ^16.0 ^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.
^ ^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.
^ 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.
^ 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.
^ ^20.0 ^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.
^ ^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.
^ 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.
^ ^23.0 ^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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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  . PMID 20819078. doi:10.1042/BJ20100859.

延伸阅读

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.
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.
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.
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.
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.
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.
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.
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.

外部链接

醫學主題詞表（MeSH）：IGF-1+Receptor

[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.

[refGRCh38Ensembl-3] 3.0 ^3.1 ^3.2 GRCh38: Ensembl release 89: ENSG00000140443 - Ensembl, May 2017

[refGRCm38Ensembl-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.

[#1-7] 7.0 ^7.1 存档副本. [2018-10-18]. （原始内容存档于2020-11-30）.

[Gregory-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  . PMID 26628682. doi:10.1126/scisignal.aaa6711.

[pmid7758431-10] 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.

[pmid7540132-11] 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.

[pmid11724822-12] 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  . PMID 11724822. doi:10.1083/jcb.200106139.

[pmid10026153-13] 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.

[pmid18632619-14] 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.

[pmid11423532-15] 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.

[pmid12697834-16] 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  . PMID 12697834. doi:10.1128/mcb.23.9.3363-3372.2003.

[pmid8776723-17] 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.

[pmid9506989-18] 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.

[pmid8764099-19] 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.

[pmid10082579-20] 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  . PMID 10082579.

[pmid7559507-21] 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.

[pmid9415396-22] 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.

[pmid7642582-23] 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.

[pmid16113100-24] 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.

[pmid9727029-25] 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.

[pmid11071852-26] 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.

[pmid9111084-27] 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.

[pmid20819078-28] 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  . PMID 20819078. doi:10.1042/BJ20100859.

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胰岛素样生长因子1受体

目录

结构

相互作用

调控

相关条目

参考文献

延伸阅读

外部链接