Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor.
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.
Soker
S
S
Department of Surgery, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Takashima
S
S
Miao
H Q
HQ
Neufeld
G
G
Klagsbrun
M
M
D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D002460:Cell Line / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D002633:Chemotaxis / Q000502:physiology; D003001:Cloning, Molecular; D016228:Endothelial Growth Factors / Q000737:chemistry / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000737:chemistry* / Q000166:cytology; D005091:Exons / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D007536:Isomerism; D008222:Lymphokines / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D039942:Neuropilin-1; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D011975:Receptors, Mitogen / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014470:Umbilical Cord / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000954:Antigens, Surface; D016228:Endothelial Growth Factors; D008222:Lymphokines; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D011975:Receptors, Mitogen; D011993:Recombinant Fusion Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D039942:Neuropilin-1; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor