胰島素樣生長因子1受體
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,屬於酪胺酸激酶受體家族。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
[編輯]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醣基化、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,與胞內的訊息傳遞有關。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和胰島素樣生長因子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,參與酪胺酸的自我磷酸化。酪胺酸殘基1161、1165和1166及鄰近的自我磷酸化結構被稱為IGF1R的酪胺酸激酶結構域(tyrosine kinase domain)[9]。
在於對應配體結合後,α鏈會誘導β的酪胺酸發生自我磷酸化。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
[編輯]胰島素樣生長因子1受體可與下列蛋白質相互作用:
調控
[編輯]已有報道的是IGF1R的表現水平受microRNAmiR-7負調控[28]。
相關條目
[編輯]- 胰島素受體
- Linsitinib, an inhibitor of IGF-1 in clinical trials for cancer treatment
參考文獻
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- ^ 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.
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