Vav proteins in cancer

The Vav family of proto-oncogenes, Vav1-3, represent a subgroup within the Dbl family of guanine nucleotide exchange factors (GEF), which are regulated by tyrosine phosphorylation and mediate the activation of Rho/Rac GTP-binding proteins downstream of numerous cell surface receptors that either have intrinsic tyrosine kinase activity or associate with nonreceptor tyrosine kinases (e.g., members of the Src family). Additionally, these Vav GEFs possess additional protein:protein interaction domains that allow them to participate in several other signaling pathways upon recruitment and activation at the plasma membrane. Recent work on Vav GEFs has demonstrated their contribution to multiple human malignancies through regulation of cell motility, survival, angiogenesis, and proliferation. In general, these effects arise from ectopic expression (Vav1), upregulation (Vav1 and Vav3), or continuous activation of Vav proteins by deregulated receptor and non-receptor tyrosine kinases (all three isoforms). This chapter will address the physiological functions of Vav proteins, their mechanism of regulation, and their emerging roles as regulators of human tumorigenesis.