DIFFERENTIAL REGULATIONS OF PHOSPHATIDYLCHOLINE BIOSYNTHESIS IN U937 CELLS BY INHIBITORS OF PROTEIN AND TYROSINE KINASES

1. The differential effects of inhibitors of protein kinase (PK) or tyrosine kinase (TK) on phosphatidylcholine (PC) biosynthesis in monocyte-like U937 cells were compared in pulse-chase studies in which the cells prelabelled with [H-3]choline for 30 min were chased in the absence or presence of kinase inhibitors. 2. PKA inhibitor (H-89) decreased the label incorporation into PC, while PKA activator (8-BrcAMP) had no effect. 3. PKC inhibitors (chelerythrine and hypericin) inhibited PC biosynthesis; on the other hand, PKC activator (SC-10) was stimulatory. 4. The inhibition of PC biosynthesis by H-89 and chelerythrine was accompanied by the inactivation of CTP: cholinephosphate cytidylyltransferase (CT). 5. In contrast, TK inhibitor (genistein) markedly stimulated CT and PC biosynthesis, while erbstatin and tyrphostin No. 25 showed no effect.