c-Abl kinase regulates the protein binding activity of c-Crk

EMBO J. 1994 May 15;13(10):2341-51.

Abstract

c-Crk is a proto-oncogene product composed largely of Src homology (SH) 2 and 3 domains. We have identified a kinase activity, which binds to the first Crk SH3 domain and phosphorylates c-Crk on tyrosine 221 (Y221), as c-Abl. c-Abl has a strong preference for c-Crk, when compared with common tyrosine kinase substrates. The phosphorylation of c-Crk Y221 creates a binding site for the Crk SH2 domain. Bacterially expressed c-Crk protein lacks phosphorylation on Y221 and can bind specifically to several proteins, while mammalian c-Crk, which is phosphorylated on tyrosine, remains uncomplexed. The protein binding activity of c-Crk is therefore likely regulated by a mechanism similar to that of the Src family kinases. v-Crk is truncated before c-Crk Y221 and forms constitutive complexes with c-Abl and other proteins. Our results suggest that c-Abl regulates c-Crk function and that it could be involved in v-Crk transformation.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Sequence
  • Animals
  • Arginine / metabolism
  • GRB2 Adaptor Protein
  • Mice
  • Models, Biological
  • Molecular Sequence Data
  • Oncogene Protein v-crk
  • Phosphorylation
  • Protein Binding
  • Protein Kinases / metabolism
  • Protein-Tyrosine Kinases / metabolism*
  • Proteins / metabolism
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-abl / metabolism*
  • Proto-Oncogene Proteins c-crk
  • Retroviridae Proteins, Oncogenic / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • GRB2 Adaptor Protein
  • Grb2 protein, mouse
  • Oncogene Protein v-crk
  • Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-crk
  • Retroviridae Proteins, Oncogenic
  • Arginine
  • Protein Kinases
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-abl