Transmembrane signaling by interferon a involves diacylglycerol production and activation of the e isoform of protein kinase C in Daudi cells

The early events that occur after treatment of the highly Interferon α (IFN-α)-sensitive human lymphoblastoid Daudi cell line with human leukocyte IFN-α have been examined. IFN-α treatment of Daudi cells results in a rapid and transient increase in the cellular content of diacykdycerol, which occurs In the absence of inosftol pbospholipid turnover, or an increase in intracellular calcium concentration. Furthermore, IFN-α treatment results in a selective, time-dependent activation of the Ca²⁺-independent ε isoform of protein kinase C (PKC), while the a isoform is unaffected by IFN-α treatment. In contrast, IFN-α treatment of an IFN-resistant subclone of Daudi cells had no effect on the diacylglycerol content of cells and on the activation of PKC-ε. The selective PKC inhibitor staurosporine blocked the transcriptional activation of IFN-α-stimulated genes, the cytoplasmic accumulation of mRNAs for these genes, and the induction of antiviral activity by IFN-α against vesicular stomatitis virus in IFN-sensitive cells. These observations suggest that transmembrane signaling of IFN-α involves diacylglycerol production and activation of PKC-ε in Daudi cells.