Molecules in focus: Cytosolic phospholipase A2-α

Cytosolic phospholipase A2-α (cPLA2-α) cleaves its preferred substrate, arachidonic acid, at the sn-2 position of membrane glycerophospholipids. Stimulation of cells with agents that mobilize intracellular calcium and/or promote the phosphorylation of cPLA2-α leads to (i) translocation of the enzyme from cytosol to endoplasmic reticulum, Golgi apparatus and perinuclear membranes—where it associates with the arachidonic acid in close proximity to downstream eicosanoid-producing enzymes; and (ii) the change in configuration induced by phosphorylation increases the phospholipid binding affinity and arachidonic acid release. As a mediator of growth factors, cytokines, chemokines, and hormones that modulate survival and growth in various cell types, cPLA2-α has attracted considerable attention as a potential therapeutic target in control of inflammation and cancer. The importance of the enzyme may have been underestimated by the relatively normal phenotype in the enzyme knockout animals. A clear phenotype has emerged when these knockout animals are used as models of various diseases.