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

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.