Abstract
Vascular endothelial growth factor (VEGF), a major regulator of angiogenesis, binds to two receptor tyrosine kinases, KDR/Flk-1 and Flt-1. We now describe the purification and the expression cloning from tumor cells of a third VEGF receptor, one that binds VEGF165 but not VEGF121. This isoform-specific VEGF receptor (VEGF165R) is identical to human neuropilin-1, a receptor for the collapsin/semaphorin family that mediates neuronal cell guidance. When coexpressed in cells with KDR, neuropilin-1 enhances the binding of VEGF165 to KDR and VEGF165-mediated chemotaxis. Conversely, inhibition of VEGF165 binding to neuropilin-1 inhibits its binding to KDR and its mitogenic activity for endothelial cells. We propose that neuropilin-1 is a novel VEGF receptor that modulates VEGF binding to KDR and subsequent bioactivity and therefore may regulate VEGF-induced angiogenesis.
Publication types
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, P.H.S.
MeSH terms
- Antigens, Surface / genetics
- Antigens, Surface / metabolism
- Cell Line / chemistry
- Cell Line / cytology
- Cell Line / metabolism
- Chemotaxis / physiology
- Cloning, Molecular
- Endothelial Growth Factors / chemistry
- Endothelial Growth Factors / metabolism*
- Endothelium, Vascular / chemistry*
- Endothelium, Vascular / cytology
- Exons / physiology
- Gene Expression
- Humans
- Isomerism
- Lymphokines / chemistry
- Lymphokines / metabolism*
- Molecular Sequence Data
- Neovascularization, Physiologic / physiology
- Nerve Tissue Proteins / genetics*
- Nerve Tissue Proteins / metabolism*
- Neuropilin-1
- RNA, Messenger / metabolism
- Receptor Protein-Tyrosine Kinases / genetics
- Receptor Protein-Tyrosine Kinases / isolation & purification
- Receptor Protein-Tyrosine Kinases / metabolism
- Receptors, Growth Factor / genetics
- Receptors, Growth Factor / isolation & purification
- Receptors, Growth Factor / metabolism
- Receptors, Mitogen / genetics
- Receptors, Mitogen / isolation & purification
- Receptors, Mitogen / metabolism
- Receptors, Vascular Endothelial Growth Factor
- Recombinant Fusion Proteins / genetics
- Recombinant Fusion Proteins / metabolism
- Umbilical Cord / cytology
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factors
Substances
- Antigens, Surface
- Endothelial Growth Factors
- Lymphokines
- Nerve Tissue Proteins
- RNA, Messenger
- Receptors, Growth Factor
- Receptors, Mitogen
- Recombinant Fusion Proteins
- VEGFA protein, human
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factors
- Neuropilin-1
- Receptor Protein-Tyrosine Kinases
- Receptors, Vascular Endothelial Growth Factor
Associated data
- GENBANK/AF016050
- GENBANK/AF016098