Neuropilin-1 is a placenta growth factor-2 receptor

被引:256
作者
Migdal, M
Huppertz, B
Tessler, S
Comforti, A
Shibuya, M
Reich, R
Baumann, H
Neufeld, G [1 ]
机构
[1] Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel
[2] Hebrew Univ Jerusalem, Dept Pharmacol, IL-91120 Jerusalem, Israel
[3] RWTH Aachen, D-52074 Aachen, Germany
[4] Univ Tokyo, Inst Med Sci, Dept Genet, Minato Ku, Tokyo 108, Japan
关键词
D O I
10.1074/jbc.273.35.22272
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Placenta growth factor (PIGF) belongs to the family of vascular endothelial growth factors (VEGFs). It binds to the flt-1 VEGF receptor but not to the KDR/flk-1 receptor which is thought to mediate most of the angiogenic and proliferative effects of VEGF, Three PIGF isoforms are produced by alternative splicing. PlGF-1 and PlGF-3 differ from PlGF-2 since they lack the exon 6 encoded peptide which bestows upon PlGF-2 its heparin binding properties. Cross-linking experiments revealed that I-125-PlGF-2 binds to two endothelial cell surface receptors in a heparin dependent fashion. The binding of I-125-PlGF-2 to these receptors was inhibited by an excess of PlGF-2 and by the 165-amino acid form of VEGF (VEGF(165)), but not at all by VEGF(165) and very marginally if at all by PlGF-1, The apparent molecular weight and the binding characteristics of these receptors correspond to those of the recently identified VEGF(165) specific receptor neuropilin-1, and we therefore conclude that neuropilin-1 is a receptor for PlGF-2. The binding of I-125-PlGF-2 as well as the binding of I-125-VEGF(165) to these receptors was inhibited by a synthetic peptide derived from exon 6 of PlGF. Furthermore, the binding of I-125-PIGF-2, but not that of I-125-VEGF(165), was also inhibited by a synthetic peptide derived from exon 7 of PlGF. These observations indicate that the peptides encoded by these exons probably participate in the formation of the domain which mediates the binding of PlGF-2 to these receptors, We have also determined, using chemically modified heparin species, that the presence of sulfate moieties on the glucosamine-O-6 and on the iduronic acid-O-2 groups of heparin was required for the potentiation of I-125-PlGF-2 binding to these receptors. To determine if PlGF-2 is able to induce biological responses that are not induced by PlGF-1, we compared the effects of PlGF-1 and PlGF-2 on the migration and proliferation of endothelial cells. Both PlGF forms induced migration of endothelial cells. However, there was no quantitative difference between the response to PIGF-2 and the response to PIGF-1. Furthermore, neither PIGF-1 nor PlGF-2 had any effect upon the proliferation of the endothelial cells.
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页码:22272 / 22278
页数:7
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