Vascular endothelial growth factor increases urokinase receptor expression in vascular endothelial cells

Mandriota, Stefano Jacopo; Seghezzi, G.; Vassalli, Jean-Dominique; Ferrara, N.; Wasi, S.; Mazzieri, R.; Mignatti, P.; Pepper, Michael Sean

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Title		Vascular endothelial growth factor increases urokinase receptor expression in vascular endothelial cells
Authors		Mandriota, Stefano Jacopo Seghezzi, G. Vassalli, Jean-Dominique Ferrara, N. Wasi, S. Mazzieri, R. Mignatti, P. Pepper, Michael Sean
Published in		Journal of Biological Chemistry. 1995, vol. 270, no. 17, p. 9709-9716
Abstract		Vascular endothelial growth factor (VEGF) is a potent angiogenic factor and endothelial cell-specific mitogen that stimulates urokinase-type plasminogen activator (uPA) activity in vascular endothelial cells. Here, we report that VEGF increases the high affinity binding of uPA to the same cells and that this binding is prevented by a peptide corresponding to the uPA receptor (uPAR) binding growth factor-like domain of uPA. Ligand cross-linking, ligand blotting, and uPA-Sepharose affinity chromatography revealed an increase in a cell surface uPA binding protein that corresponds to the uPAR on the basis of its affinity for uPA, M(r) of 50,000-55,000, and phosphatidylinositol-specific phospholipase C sensitivity. By Scatchard analysis, VEGF increased the number of uPAR molecules by 2.8-3.5-fold and concomitantly decreased their affinity for uPA. By northern blotting uPAR mRNA was increased in a dose- and time-dependent manner in response to VEGF. Taken together, these findings demonstrate that VEGF-induced angiogenesis is accompanied by increased uPAR expression and uPA activity on the endothelial cell surface. These observations are consistent with the notion that the uPA-uPAR interaction facilitates cellular invasion.
Keywords		Animals — Cattle — Cells, Cultured — Endothelial Growth Factors/ physiology — Endothelium, Vascular/cytology/ metabolism — Enzyme Activation — Lymphatic System/cytology/metabolism — Lymphokines/ physiology — Phosphatidylinositol Diacylglycerol-Lyase — Phosphoinositide Phospholipase C — Phosphoric Diester Hydrolases/metabolism — RNA, Messenger/genetics/metabolism — Receptors, Cell Surface/ biosynthesis/genetics — Receptors, Urokinase Plasminogen Activator — Urokinase-Type Plasminogen Activator/metabolism — Vascular Endothelial Growth Factor A — Vascular Endothelial Growth Factors
Identifiers		PMID: 7730348
Full text		Article - Limited access to UNIGE Other version: http://www.jbc.org/content/270/17/9709.full.pdf
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine
Citation (ISO format)		MANDRIOTA, Stefano Jacopo et al. Vascular endothelial growth factor increases urokinase receptor expression in vascular endothelial cells. In: Journal of Biological Chemistry, 1995, vol. 270, n° 17, p. 9709-9716. https://archive-ouverte.unige.ch/unige:8881