INTERLEUKIN-2 STIMULATES A LATE INCREASE IN PHOSPHATIDIC-ACID PRODUCTION IN THE ABSENCE OF PHOSPHOLIPASE-D ACTIVATION

The signal transduction pathways involving phospholipid metabolism dur ing T-cell proliferation remain partly undefined. Herein me show that interleukin-2 caused a late (>12 h) rise in the intracellular phosphat idic acid content of CTLL-2 cells which mas a consequence of the activ ation of the enzyme diacylglycerol kinase, No activation of phospholip ase D mas observed at similar times. Incubation of the cells with a re cognized diacylglycerol kinase a isoform inhibitor, R59499, prior to i nterleukin-2 stimulation was able to block cell cycle entry, diacyglyc erol kinase activation and phosphatidic acid accumulation. In contrast , when R59499 was added 3 h after interleukin-2, few or no observable effects on the above three parameters were noticed. These results sugg est that the early signaling employed by IL-2 involving the a isoform of diacylglycerol kinase is sufficient to control the late increase in phosphatidic acid and that phosphatidic acid is a mitogenic agent in T-cells. (C) 1998 Federation of European Biochemical Societies.