EFFECTS OF ARA-C ON NEUTRAL SPHINGOMYELINASE AND MITOGEN-ACTIVATED AND STRESS-ACTIVATED PROTEIN-KINASES IN T-LYMPHOCYTE CELL-LINES

Neutral sphingomyelinase (SMase)(1) can be activated by extracellular signals to produce ceramide, which may affect mitogen-activated protei n kinase (MAPK) activities. Neutral SMase activity was assessed in mem branes from Jurkat, a human T-cell line, and EL4, a murine T-cell line . Ara-C activated SMase within 10 minutes in both Jurkat and ELA cells , while phorbol ester (PMA) had no effect. PMA, but not Ara-C or ceram ides, activated ERK MAPKs in Jurkat and EL4. PMA acted synergistically with ionomycin to activate JNK MAPKs in Turkat and EL4 within 10 minu tes. Ara-C activated JNKs only after prolonged incubation (90-120 minu tes). Thus, ceramide is not a positive signal for ERK activation in T- cell lines. The effects of Ara-C on JNK activity may be mediated throu gh secondary response pathways.