Protein kinase C is required for induction of 2',5'-oligoadenylate synthetases.
Induction of the p40/46 and p69/71 isoforms of the 2',5'-oligoadenylate (2-5A) synthetase by interferon-alpha (IFN-alpha) is variable among six different Burkitt lymphoma cell lines with Ramos cells expressing among the highest levels of these enzymes. Inhibitors of protein kinase C (PKC) block induction of mRNAs encoding both isoforms; however, induction of the p69/71 isoform is more sensitive to these inhibitors. Down-regulation of PKC by prolonged treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) also blocks induction of 2-5A synthetase mRNAs and decreases both constitutive and IFN-alpha-induced enzymatic activity. Cotreatment of cells with TPA and IFN-alpha increases induction of 2-5A synthetase mRNAs above that seen in cells treated with IFN-alpha alone. IFN-alpha does not directly activate PKC-alpha or PKC-delta, the two most abundant PKC isoforms present in Ramos cells, suggesting that PKC activation by another signaling pathway is necessary for maximal induction of 2-5A synthetases by IFN-alpha.
Yu
F
F
Department of Zoology, Arizona State University, Tempe 85287-1501, USA.
Floyd-Smith
G
G
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis* / Q000235:genetics; D000470:Alkaloids; D053119:Benzophenanthridines; D002051:Burkitt Lymphoma; D004789:Enzyme Activation; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D009281:Naphthalenes / Q000494:pharmacology; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D016898:Interferon-alpha; D007527:Isoenzymes; D009281:Naphthalenes; D010617:Phenanthridines; D012333:RNA, Messenger; C016299:chelerythrine; D011493:Protein Kinase C; D015088:2',5'-Oligoadenylate Synthetase; C058819:calphostin C; D013755:Tetradecanoylphorbol Acetate