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

Seghezzi, G.
Ferrara, N.
Wasi, S.
Mazzieri, R.
Mignatti, P.
Published in The 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 AnimalsCattleCells, CulturedEndothelial Growth Factors/ physiologyEndothelium, Vascular/cytology/ metabolismEnzyme ActivationLymphatic System/cytology/metabolismLymphokines/ physiologyPhosphatidylinositol Diacylglycerol-LyasePhosphoinositide Phospholipase CPhosphoric Diester Hydrolases/metabolismRNA, Messenger/genetics/metabolismReceptors, Cell Surface/ biosynthesis/geneticsReceptors, Urokinase Plasminogen ActivatorUrokinase-Type Plasminogen Activator/metabolismVascular Endothelial Growth Factor AVascular Endothelial Growth Factors
PMID: 7730348
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Other version: http://www.jbc.org/content/270/17/9709.full.pdf
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MANDRIOTA, Stefano Jacopo et al. Vascular endothelial growth factor increases urokinase receptor expression in vascular endothelial cells. In: The Journal of biological chemistry, 1995, vol. 270, n° 17, p. 9709-9716. https://archive-ouverte.unige.ch/unige:8881

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Deposited on : 2010-07-12

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