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Structure-function analysis of VEGF receptor activation and the role of coreceptors in angiogenic signaling.
Journal article

Structure-function analysis of VEGF receptor activation and the role of coreceptors in angiogenic signaling.

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  • 2009-09-19
Published in:
  • Biochimica et biophysica acta. - 2010
Animals
Heparan Sulfate Proteoglycans
Humans
Neovascularization, Physiologic
Neuropilins
Protein Isoforms
Protein Multimerization
Protein Structure, Tertiary
Receptors, Vascular Endothelial Growth Factor
Signal Transduction
Structure-Activity Relationship
Vascular Endothelial Growth Factors
English Vascular endothelial growth factors (VEGFs) constitute a family of six polypeptides, VEGF-A, -B, -C, -D, -E and PlGF, that regulate blood and lymphatic vessel development. VEGFs specifically bind to three type V receptor tyrosine kinases (RTKs), VEGFR-1, -2 and -3, and to coreceptors such as neuropilins and heparan sulfate proteoglycans (HSPG). VEGFRs are activated upon ligand-induced dimerization mediated by the extracellular domain (ECD). A study using receptor constructs carrying artificial dimerization-promoting transmembrane domains (TMDs) showed that receptor dimerization is necessary, but not sufficient, for receptor activation and demonstrates that distinct orientation of receptor monomers is required to instigate transmembrane signaling. Angiogenic signaling by VEGF receptors also depends on cooperation with specific coreceptors such as neuropilins and HSPG. A number of VEGF isoforms differ in binding to coreceptors, and ligand-specific signal output is apparently the result of the specific coreceptor complex assembled by a particular VEGF isoform. Here we discuss the structural features of VEGF family ligands and their receptors in relation to their distinct signal output and angiogenic potential.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/68815
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