Suppression of c-Src activity by C-terminal Src kinase involves the c-Src SH2 and SH3 domains: analysis with Saccharomyces cerevisiae

Mol Cell Biol. 1993 Sep;13(9):5290-300. doi: 10.1128/mcb.13.9.5290-5300.1993.

Abstract

The kinase activity of c-Src is normally repressed in vertebrate cells by extensive phosphorylation of Y-527. C-terminal Src kinase (CSK) is a candidate for the enzyme that catalyzes this phosphorylation. We have used budding yeast to study the regulation of c-Src activity by CSK in intact cells. Expression of c-Src in Saccharomyces cerevisiae, which lacks endogenous c-Src and Y-527 kinases, induces a kinase-dependent growth inhibition. Coexpression of CSK in these cells results in phosphorylation of c-Src on Y-527 and suppression of the c-Src phenotype. CSK does not fully suppress the activity of c-Src mutants lacking portions of the SH2 or SH3 domains, even though these mutant proteins are phosphorylated on Y-527 by CSK both in vivo and in vitro. These results suggest that both the SH2 and SH3 domains of c-Src are required for the suppression of c-Src activity by Y-527 phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • CSK Tyrosine-Protein Kinase
  • Cell Division
  • DNA Mutational Analysis
  • Oncogene Protein pp60(v-src) / metabolism*
  • Phenotype
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Phosphotyrosine
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins pp60(c-src) / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae
  • Structure-Activity Relationship
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism
  • src-Family Kinases

Substances

  • Phosphoproteins
  • Recombinant Fusion Proteins
  • Phosphotyrosine
  • Tyrosine
  • Protein-Tyrosine Kinases
  • CSK Tyrosine-Protein Kinase
  • Oncogene Protein pp60(v-src)
  • Proto-Oncogene Proteins pp60(c-src)
  • src-Family Kinases