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.