The role of diacylglycerol kinase activation and phosphatidate accumulation in interleukin-2-dependent lymphocyte proliferation.
The biological effects of interleukin-2 (IL-2) were examined in T lymphocytes. IL-2 binding induced the rapid activation of diacylglycerol kinase in both cytosolic and membrane subfractions. This enzyme utilized diacylglycerol from multiple endogenous and exogenous sources for the synthesis of phosphatidic acid. Phosphatidic acid was, in turn, shown to stimulate the accumulation of c-myc mRNA and augment cellular proliferation when added to IL-2-dependent cell lines. These results link previous observations of IL-2 and glycosylphosphatidylinositol-dependent diacylglycerol production to phosphatidic acid accumulation, and suggest that diacylglycerol kinase activation is part of an intricate IL-2 signaling cascade that utilizes phosphatidic acid as an effector molecule.
Merida
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Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104-6082.
Williamson
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Smith
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Gaulton
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GN
D001483:Base Sequence; D002455:Cell Division; D002460:Cell Line; D004261:DNA Replication; D019852:Diacylglycerol Kinase; D004075:Diglycerides / Q000378:metabolism; D004789:Enzyme Activation; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D008969:Molecular Sequence Data; D010712:Phosphatidic Acids / Q000502:physiology*; D010770:Phosphotransferases / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D013347:Subcellular Fractions / Q000201:enzymology; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology*
D004075:Diglycerides; D007376:Interleukin-2; D010712:Phosphatidic Acids; D012333:RNA, Messenger; D010770:Phosphotransferases; D019852:Diacylglycerol Kinase