VAV1 Recombinant Rabbit mAb (S-2499-37)

VAV1 is a 95-kDa multidomain guanine-nucleotide exchange factor (GEF) that is expressed predominantly in hematopoietic cells; it consists of an N-terminal calponin-homology (CH) domain, an acidic region that is phosphorylated by tyrosine kinases, a Dbl-homology (DH) domain responsible for Rho/Rac GEF activity, a Pleckstrin-homology (PH) domain for membrane targeting, two SH3 domains flanking a single SH2 domain, and a C-terminal SH3 domain that mediates protein–protein interactions. Upon engagement of T- and B-cell antigen receptors, VAV1 is rapidly tyrosine-phosphorylated by Src and Syk family kinases, leading to its recruitment to the plasma membrane where it catalyzes GDP-to-GTP exchange on Rac1, Rac2, and RhoG, thereby activating downstream pathways controlling actin cytoskeletal reorganization, integrin clustering, immune-synapse formation, calcium flux, and transcriptional programs via NF-κB, NFAT, and AP-1. In addition to its canonical GEF function, phosphorylated VAV1 serves as a scaffold that binds adaptors such as SLP-76 and LAT to propagate signaling complexes, and it participates in negative feedback through interactions with ubiquitin ligases like c-Cbl. Gain-of-function mutations or overexpression of VAV1 are implicated in T-cell acute lymphoblastic leukemia, peripheral T-cell lymphomas, and neuroblastoma, whereas loss-of-function variants cause combined immunodeficiency with impaired T-cell development and function, highlighting its central role in both adaptive immunity and oncogenesis.