c-Abl kinase regulates the protein binding activity of c-Crk.
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.
Mesh Terms:
3T3 Cells, Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Arginine, GRB2 Adaptor Protein, Mice, Models, Biological, Molecular Sequence Data, Oncogene Protein v-crk, Phosphorylation, Protein Binding, Protein Kinases, Protein-Tyrosine Kinases, Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-abl, Proto-Oncogene Proteins c-crk, Retroviridae Proteins, Oncogenic
3T3 Cells, Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Arginine, GRB2 Adaptor Protein, Mice, Models, Biological, Molecular Sequence Data, Oncogene Protein v-crk, Phosphorylation, Protein Binding, Protein Kinases, Protein-Tyrosine Kinases, Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-abl, Proto-Oncogene Proteins c-crk, Retroviridae Proteins, Oncogenic
EMBO J.
Date: May. 15, 1994
PubMed ID: 8194526
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