Structure and function of vav.

The proto-oncogene vav is expressed solely in cells of hematopoietic origin regardless of their differentiation lineage. However, recently an homologue of vav, which is widely expressed (vav2) has been identified. Vav is a complicated and interesting molecule that contains a number of structural features found in proteins involved in cell signaling. Vav has a leucine-rich region, a leucine-zipper, a calponin homology domain, an acidic domain, a Dbl-homology domain, a pleckstrin homology domain, a cysteine-rich domain, two Src homology 3 domains, with a proline-rich region in the amino-SH3 domain, and finally an Src homology 2 domain. These domains have been implicated in protein protein interactions and strongly suggest that vav is involved in signaling events. vav is also rapidly and transiently tyrosine phosphorylated through the activation of multiple receptors on hematopoietic cells. Furthermore, vav is tyrosine phosphorylated upon the activation of several cytokines and growths factors. Recently, the generation of nice vav-/- showed that vav has an essential role in proliferation/activation of T and B cells. The purpose of this review is to summarize the current knowledge on vav and to evaluate the roles of vav in cellular functions.