Focal adhesion kinase (FAK) activates and stabilizes IGF-1 receptor

被引：36

作者：

Andersson, Sandra ^{[1
]}

D'Arcy, Padraig ^{[1
]}

Larsson, Olle ^{[1
]}

Sehat, Bita ^{[1
]}

机构：

[1] Karolinska Hosp, Dept Pathol & Oncol, CCK, Karolinska Inst, SE-17176 Stockholm, Sweden

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2009年 / 387卷 / 01期

关键词：

FAK; IGF-1R; Phosphorylation; Signaling; Degradation; FACTOR-I RECEPTOR; GROWTH-FACTOR RECEPTOR; TYROSINE PHOSPHORYLATION; INCREASED EXPRESSION; HUMAN BREAST; INSULIN; CELLS; CANCER; VIVO; PAXILLIN;

D O I：

10.1016/j.bbrc.2009.06.088

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：36 / 41

页数：6

共 35 条

[1]

p125Fak focal adhesion kinase is a substrate for the insulin and insulin-like growth factor-I tyrosine kinase receptors [J].