C-SRC ENHANCES THE SPREADING OF SRC- -FIBROBLASTS ON FIBRONECTIN BY AKINASE-INDEPENDENT MECHANISM/

We have explored the role of the tyrosine kinase c-Src in cellular adh esion. Fibroblasts derived from src-/- mice (src-/- fibroblasts) exhib it a reduced rate of spreading on fibronectin. This defect is rescued by expression of wild-type chicken c-Src. Analyses of mutants suggest that c-Src increases the rate of cell spreading in src-/- fibroblasts through a kinase-independent mechanism requiring both the SH3 and SH2 domains. To further address the role of c-Src in adhesion, we examined the activity and subcellular distribution of c-Src during the adhesio n of fibroblasts on fibronectin. We observed a transient increase in t he specific kinase activity of c-Src accompanied by the partial dephos phorylation of the negative regulatory site Y527. Activation of c-Src is followed by its redistribution to newly formed focal adhesions. The se results suggest that the enzymatic activity and subcellular distrib ution of c-Src are coordinately regulated during cellular adhesion and that c-Src can affect adhesion by a kinase-independent mechanism.