title: Focal adhesion kinase (FAK) activates and stabilizes IGF-1 receptor.
abstract: 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.
authors: Karolinska Institute, Department of Oncology and Pathology, Karolinska Hospital, Stockholm, Sweden.
authors: Sandra
authors: S
authors: Andersson
authors: Pádraig
authors: P
authors: D'Arcy
authors: Olle
authors: O
authors: Larsson
authors: Bita
authors: B
authors: Sehat
mesh_terms: D045744:Cell Line, Tumor; D004795:Enzyme Stability; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D017526:Receptor, IGF Type 1 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism
chemical_list: D008024:Ligands; D034741:RNA, Small Interfering; D017526:Receptor, IGF Type 1; D051416:Focal Adhesion Protein-Tyrosine Kinases