Role of cytosolic phospholipase A2 in mediating Rac signaling to JNK stimulation

다국어 초록 (Multilingual Abstract)

The 85-kDa cytosolic phospholipase A2(cPLA2), which selectively releas arachidonic acid(AA) from the sn-2 position of membrane phospholipid participates in signaling in processes such as inflammation, platelet activation, c proliferation, and cytokine-induced cytotoxicity. Recently, we and others report that cPLA2 is stimulated by activation of Rac, a member of Rho family GTPase and thus cPLA2 acts as a major downstream mediator of Rac signaling(Cell 8 849-856; Biochem. J., 326, 333-337; Biochem. J., 330, 1009-1014). In this study, w present further evidences for the essential roles of cPLA2 and subsequent A release in Rac-mediated signaling to c-fun N-terminal kinase(JNK) activation response to growth factors and cytokines. We demonstrate that eith co-transfection with antisense cPLA2 oligonucleotide or pretreatment wi mepacrine, a potent inhibitor of phospholipase A2, blocks Rac-mediated JN activation, implying a critical role of cPLA2 in Rac-signaling to JNK activation. accordance with this observation, we demonstrate that the addition of exogeno AA, a principal product of Rac-mediated PLA2, caused a dose-depende stimulation of JNK. Together, our findings suggest that phospholipase A especially cPLA2, mediates the signaling cascade by which Rac stimulates JNK.