c-Src enhances the spreading of src-/-fibroblasts on fibronectin by a kinase-independent mechanism

Kenneth B. Kaplan (Lead / Corresponding author), Jason R. Swedlow, David O. Morgan, Harold E. Varmus

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    297 Citations (Scopus)

    Abstract

    We have explored the role of the tyrosine kinase c-Src in cellular adhesion. Fibroblasts derived from src-/-mice (src-/-fibroblasts) exhibit 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 adhesion of fibroblasts on fibronectin. We observed a transient increase in the specific kinase activity of c-Src accompanied by the partial dephosphorylation of the negative regulatory site Y527. Activation of c-Src is followed by its redistribution to newly formed focal adhesions. These results suggest that the enzymatic activity and subcellular distribution of c-Src are coordinately regulated during cellular adhesion and that c-Src can affect adhesion by a kinase-independent mechanism.

    Original languageEnglish
    Pages (from-to)1505-1517
    Number of pages13
    JournalGenes and Development
    Volume9
    Issue number12
    DOIs
    Publication statusPublished - 15 Jun 1995

    Keywords

    • c-Src
    • Cellular adhesion
    • Fibronectin
    • Focal adhesions
    • Specific kinase activity
    • src-/- Fibroblasts
    • Subcellular distribution

    ASJC Scopus subject areas

    • Genetics
    • Developmental Biology

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