Ca2+/calmodulin-independent activation of calcineurin from Dictyostelium by unsaturated long chain fatty acids

This study describes a novel mode of activation for the Ca2+/calmodulin-dep endent protein phosphatase calcineurin, Using purified calcineurin from Dic tyostelium discoideum we found a reversible, Ca2+/calmodulin-independent ac tivation by the long chain unsaturated fatty acids arachidonic acid, linole ic acid, and oleic acid, which was of the same magnitude as activation by C a2+/calmodulin, Half-maximal stimulation of calcineurin occurred at fatty a cid concentrations of approximately 10 mu M with either p-nitrophenyl phosp hate or RII phosphopeptide as substrates, The methyl ester of arachidonic a cid and the saturated fatty acids palmitic acid and arachidic acid did not activate calcineurin, The activation was shown to be independent of the reg ulatory subunit, calcineurin B. Activation by Ca2+/calmodulin and fatty aci ds was not additive. In binding assays with immobilized calmodulin, arachid onic acid inhibited binding of calcineurin to calmodulin, Therefore fatty a cids appear to mimic Ca2+/calmodulin action by binding to the calmodulin-bi nding site.