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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
27
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pubmed:dateCreated |
2001-7-2
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pubmed:abstractText |
The two most abundant secreted isoforms of vascular endothelial growth factor A (VEGF(165) and VEGF(121)) are formed as a result of differential splicing of the VEGF-A gene. VEGF(165) and VEGF(121) share similar affinities at the isolated VEGF receptor (VEGFR)-2 but have been previously demonstrated to have differential ability to activate VEGFR-2-mediated effects on endothelial cells. Herein we investigate whether the recently described VEGF(165) isoform-specific receptor neuropilin-1 (Npn-1) is responsible for the difference in potency observed for these ligands. We demonstrate that although VEGFR-2 and Npn-1 form a complex, this complex does not result in an increase in VEGF(165) binding affinity. Therefore, the differential activity of VEGF(165) and VEGF(121) cannot be explained by a differential binding affinity for the complex. Using an antagonist that competes for VEGF(165) binding at the VEGFR-2.Npn-1 complex, we observe specific antagonism of VEGF(165)-meditated phosphorylation of VEGFR-2 without affecting the VEGF(121) response. These data indicate that the formation of the complex is responsible for the increased potency of VEGF(165) versus VEGF(121). Taken together, these data suggest a receptor-clustering role for Npn-1, as opposed to Npn-1 behaving as an affinity-converting subunit.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Affinity Labels,
http://linkedlifedata.com/resource/pubmed/chemical/Endothelial Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphokines,
http://linkedlifedata.com/resource/pubmed/chemical/Macromolecular Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neuropilin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Pregnancy Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Vascular Endothelial...,
http://linkedlifedata.com/resource/pubmed/chemical/VEGFA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/placenta growth factor
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
6
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pubmed:volume |
276
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
25520-31
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pubmed:dateRevised |
2009-11-25
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pubmed:meshHeading |
pubmed-meshheading:11333271-Affinity Labels,
pubmed-meshheading:11333271-Animals,
pubmed-meshheading:11333271-Binding, Competitive,
pubmed-meshheading:11333271-COS Cells,
pubmed-meshheading:11333271-Cells, Cultured,
pubmed-meshheading:11333271-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:11333271-Endothelial Growth Factors,
pubmed-meshheading:11333271-Endothelium, Vascular,
pubmed-meshheading:11333271-Humans,
pubmed-meshheading:11333271-Lymphokines,
pubmed-meshheading:11333271-Macromolecular Substances,
pubmed-meshheading:11333271-Nerve Tissue Proteins,
pubmed-meshheading:11333271-Neuropilin-1,
pubmed-meshheading:11333271-Phosphorylation,
pubmed-meshheading:11333271-Pregnancy Proteins,
pubmed-meshheading:11333271-Protein Binding,
pubmed-meshheading:11333271-Protein Conformation,
pubmed-meshheading:11333271-Receptor Protein-Tyrosine Kinases,
pubmed-meshheading:11333271-Receptors, Growth Factor,
pubmed-meshheading:11333271-Receptors, Vascular Endothelial Growth Factor,
pubmed-meshheading:11333271-Signal Transduction,
pubmed-meshheading:11333271-Vascular Endothelial Growth Factor A,
pubmed-meshheading:11333271-Vascular Endothelial Growth Factors
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pubmed:year |
2001
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pubmed:articleTitle |
Vascular endothelial growth factor receptor-2 and neuropilin-1 form a receptor complex that is responsible for the differential signaling potency of VEGF(165) and VEGF(121).
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pubmed:affiliation |
Department of Cardiovascular Research, Procter & Gamble Pharmaceuticals, Health Care Research Center, 8700 Mason-Montgomery Road, Mason, Ohio 45040, USA.
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pubmed:publicationType |
Journal Article
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