Lysophosphatidicacid (LPA), oneof thenaturallyoccurring phospholipids, stimulates cellmotility through theactivation of Rho family members, but the signaling mechanisms remain tobe elucidated. In thepresent study,we investigated the roles of p21-activated kinase 1 (PAK1) onLPA-induced focal adhesion kinase (FAK) phosphorylation and cell motility. Treatment of human melanoma cells A2058 with LPA increased phosphorylation and activation of PAK1, which was blocked by treatment with pertussis toxin and by inhibition of phosphoinositide 3-kinase (PI3K) with an inhibitor LY294002 or by overexpression of catalytically inactive mutant of PI3Kc, indicating that LPA-induced PAK1 activation was mediated via a Gi protein and the PI3Kcsignalingpathway
