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-α (IFN-α) 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. Downregulation 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-α-induced enzymatic activity. Cotreatment of cells with TPA and IFN-α increases induction of 2-5A synthetase mRNAs above that seen in cells treated with IFN-α alone. IFN-α does not directly activate PKC-α or PKC-δ, 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-α.