Identification and localization of heparin-binding region of snake venom VEGF and its blocking of VEGF-A165.
Vascular endothelial growth factor (VEGF-A165) displays diverse effects through binding to its receptor, KDR (kinase domain-containing receptor). Heparan sulfate/heparin-like molecules greatly contribute to their interaction. Indeed, the mitogenic potency of VEGF-A165 lacking the C-terminal heparin-binding region is less than 1% compared with intact VEGF-A165. We previously found novel heparin-binding VEGFs, designated VEGF-F that specifically recognizes KDR in snake venoms. VEGF-Fs almost completely lack the C-terminal heparin-binding region compared with VEGF-A165, despite their heparin-binding potential. In this study, we attempted to identify the heparin-binding region of VEGF-F using synthetic peptides. We have demonstrated that the heparin-binding site of VEGF-F is located in its C-terminal region, particularly localized on the N-terminal portion of this region. Furthermore, a synthetic peptide of this region blocks the biological activity of VEGF-A165 in vitro and in vivo.
Tokunaga
Yuko
Y
Department of Biochemistry, Meiji Pharmaceutical University, Noshio, Kiyose, Tokyo, Japan.
Yamazaki
Yasuo
Y
Morita
Takashi
T
D000818:Animals; D001665:Binding Sites; D006493:Heparin / Q000378:metabolism* / Q000494:pharmacology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012910:Snake Venoms / Q000737:chemistry*; D012911:Snakes; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism*
D010446:Peptide Fragments; D012910:Snake Venoms; D042461:Vascular Endothelial Growth Factor A; C511613:vascular endothelial growth factor A (138-165); D006493:Heparin