c-Src enhances the spreading of src-/- fibroblasts on fibronectin by a kinase-independent mechanism.
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. These 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.
Kaplan
K B
KB
Department of Microbiology and Immunology, University of California, San Francisco 94143, USA.
Swedlow
J R
JR
Morgan
D O
DO
Varmus
H E
HE
D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D002448:Cell Adhesion; D002461:Cell Line, Transformed; D048429:Cell Size; D002645:Chickens / Q000235:genetics; D005347:Fibroblasts / Q000502:physiology*; D005353:Fibronectins; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D019000:Phosphotyrosine; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000172:deficiency / Q000502:physiology*; D013347:Subcellular Fractions / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D019061:src-Family Kinases
D005353:Fibronectins; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D016392:Proto-Oncogene Proteins pp60(c-src); D019061:src-Family Kinases