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胰岛素样生长因子1受体

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维基百科,自由的百科全书
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
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(人类
15號染色體
染色体15號染色體[3]
15號染色體
胰岛素样生长因子1受体的基因位置
胰岛素样生长因子1受体的基因位置
基因座15q26.3起始98,648,539 bp[3]
终止98,964,530 bp[3]
RNA表达模式


查阅更多表达数据
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

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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

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胰岛素样生长因子1受体可与下列蛋白质相互作用

调控

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已有报道的是IGF1R的表达水平受microRNAmiR-7负调控[28]

相关条目

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参考文献

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  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
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  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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外部链接

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