Emerging components of the Crk oncogene product: the first identified adaptor protein.

v-Crk, identified as an oncogene product of the CT10 retrovirus, became the first example of an adaptor protein. It consists mostly of the Src homology 2 (SH2) and Src homology 3 (SH3) domains. Two of the three major proteins bound to Crk SH2 have been identified as paxillin and p130Cas. Both paxillin and p130Cas are phosphorylated upon stimulation by integrin, suggesting that Crk transduces signals from integrin. The cloning of the complementary DNA of two major proteins bound to Crk SH3 was recently completed. Both cDNAs encoded novel proteins: C3G, a guanine nucleotide exchange protein for Rap1, and DOCK180, an SH3-containing protein of unknown function. The SH3 domain of Crk also binds to Sos, Abl, and Eps15. The variety of the proteins bound to Crk SH3 implies that Crk provides a set of effector proteins that are triggered together. Alternatively, other domains of the SH3-binding proteins enable Crk to specifically activate each of the SH3-binding proteins according to the particular form of stimulation.