Association of the amino-terminal half of c-Src with focal adhesions alters their properties and is regulated by phosphorylation of tyrosine 527

Kenneth B. Kaplan, Kirsten B. Bibbins, Jason R. Swedlow, Martha Arnaud, David O. Morgan, Harold E. Varmus

Research output: Contribution to journalArticle

218 Scopus citations

Abstract

We have characterized the mechanism by which the subcellular distribution of c-Src is controlled by the phosphorylation of tyrosine 527. Mutation of this tyrosine dramatically redistributes c-Src from endosomal membranes to focal adhesions. Redistribution to focal adhesions occurs independently of kinase activity and cellular transformation. In cells lacking the regulatory kinase (CSK) that phosphorylates tyrosine 527, c-Src is also found predominantly in focal adhesions, confirming that phosphorylation of tyrosine 527 affects the location of c-Src inside the cell. The first 251 amino acids of c-Src are sufficient to allow association with focal adhesions, indicating that at least one signal for positioning c-Src in focal adhesions resides in the amino-terminal half. Point mutations and deletions in the first 251 amino acids of c-Src reveal that association with focal adhesions requires the myristylation site needed for membrane attachment, as well as the SH3 domain. Expression of the aminoterminal region alters both the structural and biochemical properties of focal adhesions. Focal adhesions containing this non-catalytic portion of c-Src are larger and exhibit increased levels of phosphotyrosine staining. Our results suggest that c-Src may regulate focal adhesions and cellular adhesion by a kinase-independent mechanism.

Original languageEnglish (US)
Pages (from-to)4745-4756
Number of pages12
JournalEMBO Journal
Volume13
Issue number20
StatePublished - 1994
Externally publishedYes

Keywords

  • Focal adhesions
  • SH2
  • SH3
  • src

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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    Kaplan, K. B., Bibbins, K. B., Swedlow, J. R., Arnaud, M., Morgan, D. O., & Varmus, H. E. (1994). Association of the amino-terminal half of c-Src with focal adhesions alters their properties and is regulated by phosphorylation of tyrosine 527. EMBO Journal, 13(20), 4745-4756.