VRAP is an adaptor protein that binds KDR, a receptor for vascular endothelial cell growth factor

A protein that binds the intracellular domain of KDR (KDR-IC), a receptor f or vascular endothelial cell growth factor (VEGF), was identified by two-hy brid screening. Two-hybrid mapping showed that the VEGF receptor-associated protein (VRAP) interacted with tyrosine 951 in the kinase insert domain of HDR, Northern blot analysis identified multiple VRAP transcripts in periph eral leukocytes, spleen, thymus, heart, lung, and human umbilical vein endo thelial cells (HUVEC). The predominant VRAP mRNA encodes a 389-amino acid p rotein that contains an SH2 domain and a C-terminal proline-rich motif. In HUVEC, VEGF promotes association of VRAP with KDR, Phospholipase C gamma an d phosphatidylinositol S-kinase, effector proteins that are downstream of K DR and important to VEGF-induced endothelial cell survival and proliferativ e responses, associate constitutively with VRAP. These observations identif y VRAP as an adaptor that recruits cytoplasmic signaling proteins to KDR, w hich plays an important role in normal and pathological angiogenesis.