Vav Proteins, Adaptors and Cell Signaling

The Vav family is a group of signal transduction molecules with oncogenic potential that play important roles in development and cell signaling. Members of this family are distributed in all animal metazoans but not in unicellular organisms. Recent genomic studies suggest that the function of Vav proteins co-evolved with tyrosine kinase pathways, probably to assure the optimal conversion of extracellular signals into biological responses coupled to the cytoskeleton and gene transcription. To date, the best-known function of Vav proteins is their role as GDP/GTP exchange factors for Rho/Rac molecules, a function strictly controlled by tyrosine phosphorylation. Recent publications indicate that this function is highly dependent on the interaction of adaptor proteins that aid in the proper phosphorylation of Vav proteins, their interaction with other signaling molecules, and in modulating the strength of their signal outputs. In addition to the function of Vav proteins as exchange factors, there is increasing evidence suggesting that Vav proteins can mediate other cellular functions independently of their exchange activities, probably by working themselves as adaptor molecules. In this review, we will give a summary of the recent advances in this field, placing special emphasis on the non-catalytic roles of Vav and its interaction with other adaptor molecules.