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。

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^[1]
為以下藥物的標靶
色瑞替尼、​AP-26113、​bms-754807、​picropodophyllin^[2]
基因位置（人类） 染色体 15號染色體^[3] 基因座 15q26.3 起始 98,648,539 bp^[3] 终止 98,964,530 bp^[3]
基因位置（小鼠） 染色体 小鼠7号染色体^[4] 基因座 7 C|7 37.27 cM 起始 67,602,575 bp^[4] 终止 67,883,416 bp^[4]
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
物種	人類	小鼠
Entrez	3480	16001
Ensembl	ENSG00000140443	ENSMUSG00000005533
UniProt	P08069	Q60751
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 Mb	Chr 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

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：

• ARHGEF12,^[12]
• C-src tyrosine kinase,^[13]
• Cbl gene,^[14]
• EHD1,^[15]
• GRB10,^{[16][17][18][19]}
• IRS1,^[20][17][21]
• Mdm2,^[14]
• NEDD4,^[16][14]
• PIK3R3,^[22]
• PTPN11,^[20][23]
• RAS p21 protein activator 1,^[23]
• SHC1^[17][21][24]
• SOCS2,^[25]
• SOCS3,^[26]
• YWHAE.^[27]

调控

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

相关条目

• 胰岛素受体（英语：Insulin receptor）
• Linsitinib, an inhibitor of IGF-1 in clinical trials for cancer treatment

参考文献

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. GRCh38: Ensembl release 89: ENSG00000140443 - Ensembl, May 2017
4. 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. 
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延伸阅读

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• 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)
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• 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)
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• 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= (帮助)

外部链接

• 醫學主題詞表（MeSH）：IGF-1+Receptor