Transmembrane signaling by interferon alpha involves diacylglycerol production and activation of the epsilon isoform of protein kinase C in Daudi cells.
The early events that occur after treatment of the highly interferon alpha (IFN-alpha)-sensitive human lymphoblastoid Daudi cell line with human leukocyte IFN-alpha have been examined. IFN-alpha treatment of Daudi cells results in a rapid and transient increase in the cellular content of diacylglycerol, which occurs in the absence of inositol phospholipid turnover, or an increase in intracellular calcium concentration. Furthermore, IFN-alpha treatment results in a selective, time-dependent activation of the Ca(2+)-independent epsilon isoform of protein kinase C (PKC), while the alpha isoform is unaffected by IFN-alpha treatment. In contrast, IFN-alpha treatment of an IFN-resistant subclone of Daudi cells had no effect on the diacylglycerol content of cells and on the activation of PKC-epsilon. The selective PKC inhibitor staurosporine blocked the transcriptional activation of IFN-alpha-stimulated genes, the cytoplasmic accumulation of mRNAs for these genes, and the induction of antiviral activity by IFN-alpha against vesicular stomatitis virus in IFN-sensitive cells. These observations suggest that transmembrane signaling of IFN-alpha involves diacylglycerol production and activation of PKC-epsilon in Daudi cells.
Pfeffer
L M
LM
Laboratory of Cell Physiology and Virology, Rockefeller University, New York, NY 10021-6399.
Eisenkraft
B L
BL
Reich
N C
NC
Improta
T
T
Baxter
G
G
Daniel-Issakani
S
S
Strulovici
B
B
D000470:Alkaloids / Q000494:pharmacology; D004075:Diglycerides / Q000502:physiology*; D004789:Enzyme Activation; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000502:physiology*; D007527:Isoenzymes / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology*; D017471:Receptors, Interferon; D015398:Signal Transduction; D019311:Staurosporine; D013601:T-Lymphocytes; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014762:Viral Interference / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D000470:Alkaloids; D004075:Diglycerides; D007370:Interferon Type I; D007527:Isoenzymes; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D011493:Protein Kinase C; D019311:Staurosporine