Vascular endothelial growth factor enhances the expression of urokinase receptor in human endothelial cells via protein kinase C activation

Among other proteolytic enzymes, the urokinase-type plasminogen activator ( u-PA)/plasmin cascade contributes to cell migration and the formation of ca pillary-like structures in a fibrinous exudate. The u-PA receptor (u-PAR) f ocuses protrolytical activity on the cell surface of the endothelial cell a nd hereby accelerates the pericellular matrix degradation. Vascular endothe lial growth factor (VEGF) and fibroblast growth factor (FGF)-2 enhance u-PA receptor expression in human endothelial cells. In this paper we show that the protein kinase C (PKC) inhibitors Ro31-8220 and GF109203X inhibit VEGF (165)-induced u-PAR antigen expression in human endothelial cells, whereas PKC inhibition head no effect on FGF-2-induced u-PAR antigen enhancement. I n addition, inhibition of PKC activity had no effect on VEGF(165)- or FGF-2 -induced proliferation in human endothelial cells. We conclude that VEGF(16 5) induces u-PAR via a PKC-dependent pathway, whereas proliferation is indu ced via a different pathway probably involving tyrosine phosphorylation of proteins downstream of the VEGF receptors.