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Orf virus VEGF-E NZ2 promotes paracellular NRP-1/VEGFR-2 coreceptor assembly via the peptide RPPR
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
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2008 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 22, no 8, 3078-3086 p.Article in journal (Refereed) Published
Abstract [en]

Vascular endothelial growth factors (VEGFs) interact with the receptor tyrosine kinases (RTKs) VEGFR-1, -2, and -3; neuropilins (NRPs); and heparan sulfate (HS) proteoglycans. VEGF RTKs signal to downstream targets upon ligand-induced tyrosine phosphorylation, while NRPs and HS act as coreceptors that lack enzymatic activity yet modulate signal output by VEGF RTKs. VEGFs exist in various isoforms with distinct receptor specificity and biological activity. Here, a series of mammalian VEGF-A splice variants and orf virus VEGF-Es, as well as chimeric and mutant VEGF variants, were characterized to determine the motifs required for binding to NRP-1 in the absence (VEGF-E) or presence (VEGF-A(165)) of an HS-binding sequence. We identified the carboxyterminal peptides RPPR and DKPRR as the NRP-1 binding motifs of VEGF-E and VEGF-A, respectively. RPPR had significantly higher affinity for NRP-1 than DKPRR. VEGFs containing an RPPR motif promoted HS-independent coreceptor complex assembly between VEGFR-2 and NRP-1, independent of whether these receptors were expressed on the same or separate cells grown in cocultures. Functional studies showed that stable coreceptor assembly by VEGF correlated with its ability to promote vessel formation in an embryoid body angiogenesis assay.

Place, publisher, year, edition, pages
2008. Vol. 22, no 8, 3078-3086 p.
Keyword [en]
neuropilin, angiogenesis, heparin sulfate, pox virus, vascular endothelial growth factor
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-16229DOI: 10.1096/fj.08-107219ISI: 000258089300047PubMedID: 18467594OAI: oai:DiVA.org:uu-16229DiVA: diva2:44000
Available from: 2008-05-13 Created: 2008-12-30 Last updated: 2011-06-28Bibliographically approved

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Li, XiujuanClaesson-Welsh, LenaSpillmann, Dorothe
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Department of Genetics and PathologyDepartment of Medical Biochemistry and Microbiology
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