Basic fibroblast growth factor (FGF) stimulates the proliferation, differentiation, and motility of multiple cell types. Signal transduction by FGF is mediated by high affinity FGF receptors that have autophosphorylating tyrosine kinase activity and also elicit the release of low molecular weight signaling molecules, including inositol 1,4,5-trisphosphate, diacylglycerol, and arachidonate. We have shown previously that basic FGF-stimulated, phospholipase A (PLA)-mediated arachidonate release regulates endothelial cell (EC) motility (Sa, G., and Fox, P. L.(1994) J. Biol. Chem. 269, 3219-3225). Here we identify the phospholipase responsible for basic FGF-mediated arachidonate release as cytosolic PLA (cPLA) by demonstrating in EC lysates a requirement for micromolar Ca, dithiothreitol insensitivity, and inactivation by anti-cPLA antiserum. The role of cPLA is also indicated by the observed mechanisms of activation which show a requirement for p42 mitogen-activated protein kinase activity, cPLA phosphorylation, and cPLA translocation from cytosol to membranes. Phosphorylation of cPLA, arachidonate release from prelabeled intact cells, and cell motility all have similar concentration dependencies on basic FGF. Since arachidonate release is required for basic FGF-stimulated motility of EC, our results show that p42 mitogen-activated protein kinase activation of cPLA may be a regulatory event in stimulation of cellular release of this important eicosanoid precursor during cellular responses to basic FGF.

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