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

Li Wha Wu, Lindsey D. Mayo, James D. Dunbar, Kelly M. Kessler, Osman Nidai Ozes, Robert S. Warren, David B. Donnert

Research output: Contribution to journalArticlepeer-review

101 Citations (Scopus)

Abstract

A protein that binds the intracellular domain of KDR (KDR-IC), a receptor for vascular endothelial cell growth factor (VEGF), was identified by two-hybrid screening. Two-hybrid mapping showed that the VEGF receptor- associated protein (VRAP) interacted with tyrosine 951 in the kinase insert domain of KDR. Northern blot analysis identified multiple VRAP transcripts in peripheral leukocytes, spleen, thymus, heart, lung, and human umbilical vein endothelial cells (HUVEC). The predominant VRAP mRNA encodes a 389-amino acid protein that contains an SH2 domain and a C-terminal proline-rich motif. In HUVEC, VEGF promotes association of VRAP with KDR. Phospholipase C gamma and phosphatidylinositol 3-kinase, effector proteins that are downstream of KDR and important to VEGF-induced endothelial cell survival and proliferative responses, associate constitutively with VRAP. These observations identify VRAP as an adaptor that recruits cytoplasmic signaling proteins to KDR, which plays an important role in normal and pathological angiogenesis.

Original languageEnglish
Pages (from-to)6059-6062
Number of pages4
JournalJournal of Biological Chemistry
Volume275
Issue number9
DOIs
Publication statusPublished - 2000 Mar 3

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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