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.
Feller
S M
SM
Laboratory of Molecular Oncology, Rockefeller University, New York, NY 10021.
Knudsen
B
B
Hanafusa
H
H
D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000378:metabolism; D051380:GRB2 Adaptor Protein; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D050736:Oncogene Protein v-crk; D010766:Phosphorylation; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D050737:Proto-Oncogene Proteins c-crk; D015682:Retroviridae Proteins, Oncogenic / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; C495949:Grb2 protein, mouse; D050736:Oncogene Protein v-crk; D011506:Proteins; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D015682:Retroviridae Proteins, Oncogenic; D001120:Arginine; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl