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.
Andersson
Sandra
S
Karolinska Institute, Department of Oncology and Pathology, Karolinska Hospital, Stockholm, Sweden.
D'Arcy
Pádraig
P
Larsson
Olle
O
Sehat
Bita
B
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
D008024:Ligands; D034741:RNA, Small Interfering; D017526:Receptor, IGF Type 1; D051416:Focal Adhesion Protein-Tyrosine Kinases