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PMID:9529250

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Citation

Soker, S, Takashima, S, Miao, HQ, Neufeld, G and Klagsbrun, M (1998) Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell 92:735-45

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.

Links

PubMed

Keywords

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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:VGFR2

enables

GO:0005172: vascular endothelial growth factor receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O14786

F

Seeded From UniProt

complete

HUMAN:VEGFA

enables

GO:0005172: vascular endothelial growth factor receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O14786

F

Seeded From UniProt

complete

HUMAN:NRP1

enables

GO:0019838: growth factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P15692-4

F

Seeded From UniProt

complete

HUMAN:NRP1

involved_in

GO:0009887: animal organ morphogenesis

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete


See also

References

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