Role of PLCg and Ca in VEGF- and FGF-induced choroidal endothelial cell proliferation

McLaughlin, A. P., and G. W. De Vries. Role of PLCg and Ca21 in VEGFand FGF-induced choroidal endothelial cell proliferation. Am J Physiol Cell Physiol 281: C1448–C1456, 2001.—Although both vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) receptors have been shown to be important in the regulation of vascular endothelial cell growth, the roles of phospholipase C (PLC)g and Ca21 in their downstream signaling cascades are still not clear. We have examined the effects of VEGF and FGF on PLCg phosphorylation and on changes in intracellular Ca21 levels in primary endothelial cells. VEGF stimulation leads to PLCg activation and increases in intracellular Ca21, which are correlated with mitogen-activated protein (MAP) kinase (MAPK) activation and cell growth. Inhibition of Ca21 increases by the Ca21 chelator 1,2-bis(2-aminophenoxy) ethane-N,N,N9,N9-tetraacetic acid (BAPTA)-AM resulted in marked inhibition of MAPK activation, which was shown to be linked to regulation of cell growth in these cells. In contrast, FGF stimulation did not lead to PLCg activation or to changes in intracellular Ca21 levels, although MAPK phosphorylation and stimulation of cell proliferation were observed. Neither BAPTA-AM nor the PLC inhibitor U-73122 had an effect on these FGF-stimulated responses. These data demonstrate a direct role for PLCg and Ca21 in VEGFregulated endothelial cell growth, whereas this signaling pathway is not linked to FGF-mediated effects in primary endothelial cells. Thus endothelial cell-specific factors regulate the ability of VEGF receptors and FGF receptors to couple to this signaling pathway.