Actin-directed processes such as membrane ruffling and cell migration are regulated by specific signal transduction pathways that become activated by growth factor receptors. The same signaling pathways that lead to modifications in actin dynamics also activate cPLA(2)alpha. Moreover, arachidonic acid, the product of cPLA(2)alpha activity, is involved in regulation of actin dynamics. Therefore, it was investigated whether cPLA(2)alpha plays a role in actin dynamics, more specifically during growth factor-induced membrane ruffling and cell migration. Upon stimulation of ruffling and cell migration by growth factors, endogenous cPLA(2)alpha and its active phosphorylated form were shown to relocate at protrusions of the cell membrane involved in actin and membrane dynamics. Inhibition of cPLA(2)alpha activity with specific inhibitors blocked growth factor-induced membrane and actin dynamics, suggesting an important role for cPLA(2)alpha in these processes.