Kb. Kaplan et al., C-SRC ENHANCES THE SPREADING OF SRC- -FIBROBLASTS ON FIBRONECTIN BY AKINASE-INDEPENDENT MECHANISM/, Genes & development, 9(12), 1995, pp. 1505-1517
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.