Focal adhesion kinase and Src mediate integrin regulation of insulin receptor phosphorylation

We show here that phosphorylation of the insulin receptor and insulin recep tor substrate-1 is increased when suspended cells are replated on fibronect in. This is not due to decreased numbers of cell surface receptors, alterat ion of insulin binding, or stimulation of a phosphatase activity in non-adh erent cells. Expression of Src together with focal adhesion kinase (FAK) in suspended cells restores insulin-induced receptor autophosphorylation to l evels observed in fibronectin-attached cells. Conversely, expression of dom inant-negative mutants of either Src or FAK abolishes potentiation of insul in receptor phosphorylation by cell adhesion. The results suggest that both Src and FAK participate in integrin-mediated regulation of insulin recepto r signal. (C) 2001 Published by Elsevier Science B.V. on behalf of the Fede ration of European Biochemical Societies.