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

Kenneth B. Kaplan, Jason R. Swedlow, David O. Morgan, Harold E. Varmus

Research output: Contribution to journalArticle

292 Scopus citations

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 (US)
Pages (from-to)1505-1517
Number of pages13
JournalGenes and Development
Volume9
Issue number12
StatePublished - Jun 15 1995
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Developmental Biology
  • Genetics

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    Kaplan, K. B., Swedlow, J. R., Morgan, D. O., & Varmus, H. E. (1995). c-Src enhances the spreading of src-/-fibroblasts on fibronectin by a kinase-independent mechanism. Genes and Development, 9(12), 1505-1517.