Focal adhesion kinase (FAK) activates and stabilizes IGF-1 receptor
Focal adhesion kinase (FAK) activates and stabilizes IGF-1 receptor
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DOI：
10.1016/j.bbrc.2009.06.088
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发表时间：
2009-09-11
影响因子：
3.1
通讯作者：
Sehat, Bita
中科院分区：
文献类型：
--
作者：
Andersson, Sandra;D'Arcy, Padraig;Sehat, Bita
最近的研究表明，IGF-1R和FAK是细胞生长、存活和迁移的两个重要介质，它们之间存在直接的联系。然而，FAK影响IGF-1R功能的机制尚不清楚。本研究探讨FAK在调节IGF-1R激活和稳定中的潜在作用。研究了野生型和突变型IGF-1R的自磷酸化和磷酸化能力。令人惊讶的是，我们发现在激活环中缺少三个核心酪氨酸残基的突变IGF-1R可以被磷酸化，但它不能进行自动磷酸化，这表明另一种激酶具有磷酸化IGF-1R的能力。通过使用野生型MEF和FAK-/-MEF，我们可以证明FAK介导激活环非依赖性的磷酸化，以及Akt和ERK的激活。此外，FAK siRNA或失活会降低IGF-1R的稳定性。综上所述，我们的数据表明，FAK在IGF-1R的磷酸化、信号转导和稳定性中发挥了作用。(C)2009 Elsevier Inc.保留所有权利。
Recent studies have shown a direct association between IGF-1R and FAK, two important mediators of cell growth, survival and migration. However, the mechanism by which FAK affects IGF-1R function remains unknown. This study investigates the potential role of FAK in mediating activation and stability of IGF-1R. Autophosphorylation and phosphorylation capacities of wild type and mutant IGF-1R were Studied. Surprisingly, we found that the Mutant IGF-1R lacking the three Core tyrosine residues in the activation-loop can be phosphorylated although it is unable to undergo autophosphorylation, Suggesting that another kinase possesses the ability to phosphorylate IGF-1R. By using wild type MEFs and FAK-/- MEFs we Could demonstrate that FAK mediates activation-loop independent phosphorylation, as well as Akt and ERK activation. Furthermore, the stability of IGF-1R was decreased upon FAK siRNA or inactivation. Taken together, Our data Suggest a role for FAK in phosphorylation, signaling and stability of the IGF-1R. (C) 2009 Elsevier Inc. All rights reserved.