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

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

Research output: Contribution to journalArticle

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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
StatePublished - Mar 3 2000

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Vascular Endothelial Growth Factor Receptor
Endothelial cells
Proteins
Human Umbilical Vein Endothelial Cells
Cell growth
Vascular Endothelial Growth Factor A
Intercellular Signaling Peptides and Proteins
Phospholipase C gamma
Phosphatidylinositol 3-Kinase
Pathologic Neovascularization
Thymus
src Homology Domains
Proline
Northern Blotting
Thymus Gland
Tyrosine
Cell Survival
Screening
Leukocytes
Phosphotransferases

ASJC Scopus subject areas

  • Biochemistry

Cite this

Wu, L. W., Mayo, L., Dunbar, J. D., Kessler, K. M., Ozes, O. N., Warren, R. S., & Donnert, D. B. (2000). VRAP is an adaptor protein that binds KDR, a receptor for vascular endothelial cell growth factor. Journal of Biological Chemistry, 275(9), 6059-6062. https://doi.org/10.1074/jbc.275.9.6059

VRAP is an adaptor protein that binds KDR, a receptor for vascular endothelial cell growth factor. / Wu, Li Wha; Mayo, Lindsey; Dunbar, James D.; Kessler, Kelly M.; Ozes, Osman Nidai; Warren, Robert S.; Donnert, David B.

In: Journal of Biological Chemistry, Vol. 275, No. 9, 03.03.2000, p. 6059-6062.

Research output: Contribution to journalArticle

Wu, Li Wha ; Mayo, Lindsey ; Dunbar, James D. ; Kessler, Kelly M. ; Ozes, Osman Nidai ; Warren, Robert S. ; Donnert, David B. / VRAP is an adaptor protein that binds KDR, a receptor for vascular endothelial cell growth factor. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 9. pp. 6059-6062.
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AU - Ozes, Osman Nidai

AU - Warren, Robert S.

AU - Donnert, David B.

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N2 - 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.

AB - 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.

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