The Vav family of Rho-guanine nucleotide exchange factors, Vav1, Vav2, and Vav3, have central roles in transducing signals from cell surface receptors, such as integrin, growth factor and immune cell receptors to the cytoskeleton. This role includes receptor-mediated changes in the actin cytoskeleton and cell motility. Vav1 expression is normally restricted to hematopoietic cells, while Vav2 and Vav3 are more widely expressed. All three Vav isoforms have been shown to be abnormally expressed in several types of cancer. Vavs are composed of multiple domains, including a Dbl homology domain, a calponin homology domain, an acidic amino acid region, a pleckstrin homology domain, a cysteine-rich domain, and SH3 and SH2 domains. Vav activity is regulated by the phosphorylation status of several conserved tyrosine residues in the acidic region (In Vav2: Tyr-142, Tyr-159, and Tyr-172). These tyrosine residues are able to participate in autoinhibitory interactions with the Dbl homology domain and this interaction is prevented after phosphorylation of these sites leading to activation of Vav GEF activity.
