Vav1 functions as a GEF and scaffold protein. The domain structure and function of Vav1 is depicted. The Vav proteins encode the following domains: Calponin-homology (CH) domain—This domain is involved in Ca+2 mobilization (inset). Acidic (Ac) motif—A motif that contains 3 regulatory tyrosines in mammalian Vav and 1 in DroVav. DBL-homology (DH) domain—A conserved region that promotes the exchange of GDP for GTP on Rac/Rho GTPases, thus affecting cytoskeleton reorganization. The inset depicts the reorganization of actin during the creation of the immunologic synapse. Jurkat T cells were incubated for 15 minutes at 37°C with antigen-presenting cells (APCs) (Raji) prepulsed with medium alone (upper panel of inset) or with staphylococcus enterotoxin E (SEE) superantigen (lower panel of inset). F-actin was detected using Alexa546-coupled phalloidin (red). The cells were then analyzed by confocal microscopy. The position of the T cell and the APC (B cell) is indicated in the differential interference contrast (DIC) image by arrows. Pleckstrin homology (PH) domain—A domain that binds phosphatidylinositol 3-kinase (PI3K)–generated lipid products that enable its movement to the inner face of the plasma membrane (inset). Proline-rich region (-Pro-)—A short amino acid sequence rich in prolines that enables the binding of Vav proteins to SH3-containing proteins. SRC-homology 3 (SH3) domain—This region interacts with proteins that contain proline-rich sequences. SRC-homology 2 (SH2) domain—This domain interacts with proteins that contain phosphorylated tyrosines. Nuclear localization signal (NLS)—A motif involved in translocation to the nucleus.
