The DOI matches its Crossref record; 69 of the 69 references it cites were found in a registry or an index.
Vascular Endothelial Growth Factor Receptor-2 and Neuropilin-1 Form a Receptor Complex That Is Responsible for the Differential Signaling Potency of VEGF165 and VEGF121
Open accessAbstract
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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Cited by
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Metadata
- Authors
- Whitaker, G. B., Limberg, B. J., & Rosenbaum, J. S.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-01
- Volume
- 276
- Issue
- 27
- Pages
- 25520-25531
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2135743455
- Cited by
- 294
- References
- 69
- FWCI
- 6.08
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Whitaker, G. B., Limberg, B. J., & Rosenbaum, J. S. (2001). Vascular Endothelial Growth Factor Receptor-2 and Neuropilin-1 Form a Receptor Complex That Is Responsible for the Differential Signaling Potency of VEGF165 and VEGF121. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m102315200
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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