The v-Crk oncogene product shares homologous amino acid sequences,
designated Src homology region 2 (SH2) and SH3, with many molecules
involved in signal transduction. The v-Crk cellular homolog, c-Crk, is a member
of a newly emerging class of genes including Nck and GRB2/ASH which
encode proteins that consist primarily of SH2 and SH3 domains. Two distinct
human c-Crk cDNAs, designated Crk I and Crk II, have been identified and
shown to represent alternative splice products of c-Crk. The major translational
product of c-Crk I has been identified as a 28 kDa variably expressed
protein, while c-Crk II encodes a widely expressed 40 kDa protein and a
more variably expressed 42 kDa protein. The major c-Crk transforming
activity appears associated with c-Crk I p28 expression. DOCK 180, a 180 kDa
protein downstream of Crk, has been identified as a major Crk-associated
protein. When DOCK 180 is recruited to the plasma membrane from a cytoplasmic
reservoir, presumably by Crk, changes in cellular morphology and
spindle formation occur, suggesting DOCK 180 to be a Crk effector molecule