PHORBOL ESTERS MODULATE THE TURNOVER OF BOTH ETHER- AND ESTER-LINKED PHOSPHOLIPIDS IN CULTURED MAMMALIAN CELLS

Abstract The effects of 12- O -tetradecanoylphorbol 13-acetate (TPA) on the metabolism of ester- and ether derivatives of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were studied in HeLa and HEL-37 cells. TPA stimulated the incorporation of [ 3 H]choline into diacyl-, alkylacyl- and alkenylaclPC in HeLa cells, but inhibited the incorporation of [ 3 H]ethanolamine into the corresponding derivatives of PE. TPA also stimulated the incorporation of [ 3 H]ethanolamine into lysoPE and the release of labelled ethanolamine and phosphoethanolamine from HeLa cells prelabelled with [ 3 H]ethanolamine. All responses to TPA were abolished in HeLa cells preincubated with the phorbol ester and which were deficient in protein kinase C. In HEL-37 cells TPA stimulated label incorporation into both ester- and ether-forms of PE. The marked effects of TPA on ether-lipid metabolism raises the possibility that hydrolysis products of this class of lipid are important in transmembrane signalling pathways.