Vav-family proteins in T-cell signalling

The Vav family proteins (Vav1, Vav2, Vav3) are cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho-family GTPases. T-cell antigen receptor (TCR) signalling results in the tyrosine phosphorylation of Vav proteins and hence their activation. Results from mice deficient in one or more Vav proteins has shown that they play critical roles in T-cell development and activation. Vav1 is required for TCR-induced calcium flux, activation of the ERK MAP kinase pathway, activation of the NF-κB transcription factor, inside-out activation of the integrin LFA-1, TCR clustering, and polarisation of the T cell. Although many of these processes may require the GEF activity of Vav1, it is possible that Vav1 also has adaptor-like functions. Recent evidence suggests that Vav1 might also function in the nucleus, where it undergoes arginine methylation. An emerging theme is that Vav proteins may have important functions downstream of receptors other than the TCR, such as integrins and chemokine receptors.