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 cPLA₂ (cytosolic PLA₂) in Rat-2 fibroblasts were investigated. In the present study, we found that PMA activates cPLA₂ by a Rac-p38 kinase-dependent pathway. Consistent with this, Rac, if activated, was shown to stimulate cPLA₂ 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 cPLA₂ 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 cPLA₂. The mediatory role of p38 kinase in cPLA₂ 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 cPLA₂, anisomycin induced the translocation and activation of cPLA₂ in a p38 kinase-dependent manner.