The Vav family of Rho guanine nucleotide exchange factors (GEFs) orchestrate signaling events following lymphocyte antigen receptor activation. Vav3, like Vav (also known as Vav1 or p95Vav), undergoes tyrosine phosphorylation downstream of T cell receptor cross-linkage, and subsequently interacts with 2 adaptor molecules, SLP76 and 3BP2. Following these events, however, the paths of Vav and Vav3 diverge; Vav affects IL-2 promotor activity, while Vav3 impacts gene transcription linked to serum response element (SRE). Furthermore, Vav3 expression follows a cell cycle-dependent pattern, with transient upregulation occuring during mitosis. Encforced Vav3 expression leads to the appearance of multinucleate cells, implicating a role for Vav3 in the control of cytokinesis.