Orf virus VEGF-E NZ2 promotes paracellular NRP-1/VEGFR-2 coreceptor assembly via the peptide RPPR.

作者:	Stéphanie Cébe-Suarez, Felix S Grünewald, Rolf Jaussi, Xiujuan Li, Lena Claesson-Welsh, Dorothe Spillmann, Andrew A Mercer, Andrea E Prota, Kurt Ballmer-Hofer
语言:	ENG.
日期:	9-5-2008
学报:	The FASEB journal : official publication of the Federation of American Societies for Experimental Biology (1530-6860)
发行:	FASEB J. 8 May 2008
摘要:	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-A165) 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.-Cébe-Suarez, S., Grünewald, F. S., Jaussi, R., Li, X., Claesson-Welsh, L., Spillmann, D., Mercer, A. A., Prota, A. E., Ballmer-Hofer, K. Orf virus VEGF-E NZ2 promotes paracellular NRP-1/VEGFR-2 coreceptor assembly via the peptide RPPR.
版权:	The FASEB journal : official publication of the Federation of American Societies for Experimental Biology *Molecular Cell Biology andStructural Biology, Laboratory of Biomolecular Research, Paul Scherrer Institut, Villigen, Switzerland;Department of Genetics and Pathology, Rudbeck Laboratory, andDepartment of Medical Biochemistry and Microbiology (IMBIM), The Biomedical Center, Uppsala University, Uppsala, Sweden; and ||Virus Research Unit, Department of Microbiology and Immunology, University of Otago, New Zealand.
全文:	The FASEB journal : official publication of the Federation of American Societies for Experimental Biology (DOI) HighWire Press - (需要捐款)