Activation of phospholipase C-γ by the concerted action of tau proteins and arachidonic acid

Abstract

Phospholipase C-γ (PLC-γ) isozymes are thought to be activated by receptor-induced tyrosine phosphorylation. Proteins that activate PLC-γ1 have now been purified from bovine brain and identified as members of the tau family of microtubule-associated proteins. Activation of PLC-γ by tau was enhanced in the presence of unsaturated fatty acids such as arachidonic acid, saturated fatty acids being ineffective. Maximal (15-20-fold) activation was apparent in the presence of 0.15 μM tau and 25 μM arachidonic acid (AA). The effect of tau and AA was specific to PLC-γ isozymes in the presence of submicromolar concentrations of Ca2+ and was markedly inhibited by phosphatidylcholine. These results suggest that in cells that express tau, receptors coupled to cytosolic phospholipase A2 may activate PLC-γ isozymes indirectly in the absence of tyrosine phosphorylation through the hydrolysis of phosphatidylcholine to generate AA.