We describe the isolation and characterization of a cDNA encoding murine vav2. vav2 shares 63% and 55% identity at the nucleic acid and amino acid levels, respectively, with vav, a proto-oncogene that plays an essential role in embryonic development and hematopoietic signal transduction. The 100 kDa Vav2 protein contains the characteristic array of structural motifs found in Vav. However, unlike vav, vav2 transcripts are widely distributed in both hematopoietic and non-hematopoietic tissues. In the adult, vav2 mRNA is found at high levels in the spleen, liver, testes and placenta. Northern blot analysis reveals two vav2 mRNA species (designated alpha and beta). The alpha species is expressed throughout development while the alpha and beta species are expressed tissue-specifically in adults. Transfection of NIH3T3 cells with expression vectors containing vav2 deletions demonstrate that elimination of 183 amino terminal residues of Vav2 is sufficient to activate its oncogenic potential. Vav2-induced transformation is characterized by the appearance of foci composed of cells in which cytokinesis and karyokinesis are uncoupled. This phenotype is comparable, but not identical, to morphological changes induced by Vav and other members of the DbI family of oncoproteins. Our results suggest that Vav family members mediate functions important in the regulation of cell architecture and proliferation in most, if not all, tissues.