Regulation of cytosolic phospholipase A2 activity

The 85 kDa cytosolic phospholipase A(2) (cPLA(2)) is the key enzyme in many signaling pathways involving the release of arachidonic acid. The enzyme has been characterized in detail and contains a Ca2+-dependent lipid binding domain and a putative PH domain in addition to the catalytic domain. cPLA(2) activity is regulated to some extent at the transcriptional level, but more predominantly by phosphorylation and Ca2+. The phosphorylation is primarily mediated by MAP kinase, although also other kinases have been shown to phosphorylate cPLA(2). For activation, cPLA(2) has to be translocated to the membrane by the Ca2+-dependent lipid binding domain. Recently, we demonstrated that cPLA(2) is randomly distributed as clusters in the cytoplasm of fibroblasts. These clusters are located in close vicinity of intracellular membranes. Other studies demonstrated a perinuclear localization of cPLA(2) upon activation of cells primarily involved in inflammatory responses. The implications; of the cPLA(2) localization will be discussed with respect to regulation of cPLA(2) activity.