Phospholipase D hydrolyzes ether- and ester-linked glycerophospholipids by different pathways in MDCK cells

MDCK cells were prelabeled with 1-O-[3H]hexadecyl-2-lyso-GPC and [14C]myristic acid, which selectively labeled the glycerophospholipid subclasses with 93% of tritium in the alkyl-linked subclass and 85% of carbon-14 in the diacyl-linked subclass. By this approach, we have demonstrated that PLD upon activation via PKC pathway selectively catalyzes the degradation of ether-linked glycerophospholipid subclass. In contrast, G-protein regulatory PLD activity seems to preferentially hydrolyze ester-linked subclass. These results suggest that the selective hydrolysis of PLD action may play an important role in cellular signal transduction under physiological and pathological conditions.