Interleukin-2 stimulates a late increase in phosphatidic acid production in the absence of phospholipase D activation.
The signal transduction pathways involving phospholipid metabolism during T-cell proliferation remain partly undefined. Herein we show that interleukin-2 caused a late (> 12 h) rise in the intracellular phosphatidic acid content of CTLL-2 cells which was a consequence of the activation of the enzyme diacylglycerol kinase. No activation of phospholipase D was observed at similar times. Incubation of the cells with a recognized diacylglycerol kinase a isoform inhibitor, R59499, prior to interleukin-2 stimulation was able to block cell cycle entry, diacyglycerol 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 suggest that the early signaling employed by IL-2 involving the alpha 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.
Jones
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DR
Department of Immunology and Oncology, Centro Nacional de Biotecnologia, Consejo Superior de Investigaciones Cientificas, Cantoblanco, Madrid, Spain.
Flores
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I
Díaz
E
E
Martinez
C
C
Mérida
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I
D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D019852:Diacylglycerol Kinase / Q000037:antagonists & inhibitors; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D051379:Mice; D010712:Phosphatidic Acids / Q000096:biosynthesis*; D010739:Phospholipase D / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D052999:Quinazolinones; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007376:Interleukin-2; D007527:Isoenzymes; D010712:Phosphatidic Acids; D010880:Piperidines; D011799:Quinazolines; D052999:Quinazolinones; D011994:Recombinant Proteins; C058544:R 59949; D019852:Diacylglycerol Kinase; D010739:Phospholipase D; D013755:Tetradecanoylphorbol Acetate