Roles of Rac and p38 kinase in the activation of cytosolic phospholipase A2 in response to PMA

The roles of Rac and p38 kinase in the activation of cPLA(2) (cytosolic PLA(2)) in Rat-2 fibroblasts were investigated. In the present study, we found that PMA activates cPLA, by a Rac-p38 kinase-dependent pathway. Consistent with this, Rac, if activated, was shown to stimulate cPLA(2) in a p38 kinase-dependent manner. In another experiment to understand the signalling mechanism by which the Rac-p38 kinase cascade mediates cPLA2 activation in response to PMA, we observed that PMA-induced cPLA(2) translocation to the perinuclear region is completely inhibited by the expression of Rac1(N17) or treatment with SB203580 (inhibitor of p38 kinase), suggesting that Rac-p38 kinase cascade acts in this instance by mediating the translocation of cPLA(2). The mediatory role of p38 kinase in cPLA(2) activation was further demonstrated after a treatment with anisomycin, a very effective activator of p38 kinase. Consistent with the mediatory role of p38 kinase in stimulating cPLA(2), anisomycin induced the translocation and activation of cPLA(2) in a p38 kinase-dependent manner.