The C-terminal SH3 domain of the mouse c-Crk protein negatively regulates tyrosine-phosphorylation of Crk associated p130 in rat 3Y1 cells

Oncogene. 1994 Jun;9(6):1669-78.


We have isolated the mouse c-crk cDNA from a mouse liver cDNA library. It encodes 304 amino acids and consists mainly of SH2/SH3 regions. In Northern blot analysis, the mouse c-crk mRNA is expressed ubiquitously in every tissue and organ, suggesting that the c-Crk protein may be a common signal transducing molecule among tissues. In contrast to the v-Crk protein, which has a single SH3 domain, the c-Crk protein contains two, the more N-terminal SH3(1) domain and the C-terminal SH3(2) domain. To elucidate functions of these SH3 domains, we have constructed two c-crk mutants, B-crk and D-crk, which lack the SH3(2) and the SH3(1) domain, respectively. These mutants were expressed in rat 3Y1 cells, and examined for their transforming ability in terms of morphological phenotypes and for tyrosine phosphorylation profiles of cells expressing the mutant proteins. Morphological alteration and increased tyrosine phosphorylation of 130-140 kDa proteins, the major component of which is the Crk-associated p130, were observed in cells expressing B-Crk as well as those expressing v-Crk, but little in cells expressing c-Crk even at a similar level of expression. Although a highly tyrosine-phosphorylated form of the p130 was coimmunoprecipitated with c-Crk as well as B-Crk, the relative level of tyrosine phosphorylation of the p130, which is normalized to the amount of Crk protein immunoprecipitated, was 10 to 20 times higher in B-Crk-expressing cells than in c-Crk- or D-Crk-expressing cells. The present results indicate that the SH3(2) domain of mouse c-Crk protein negatively regulates tyrosine phosphorylation of the p130, and that lack of the SH3(2) domain in B-Crk and v-Crk may contribute, at least partly, to their morphological alteration or transforming ability through increasing tyrosine phosphorylation of the p130.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cells, Cultured
  • DNA, Complementary / chemistry
  • DNA, Complementary / isolation & purification
  • Fibroblasts / metabolism
  • Humans
  • Mice
  • Molecular Sequence Data
  • Phosphorylation
  • Protein-Tyrosine Kinases / physiology*
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-crk
  • Rats
  • Structure-Activity Relationship
  • Transfection
  • Tyrosine / metabolism*


  • Crk protein, rat
  • DNA, Complementary
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-crk
  • Tyrosine
  • Protein-Tyrosine Kinases

Associated data

  • GENBANK/S72408