Evidence for involvement of protein kinase C in the cellular response to interferon alpha.
Phospholipid/Ca2(+)-dependent protein kinase (protein kinase C; PKC) appears to be involved in the signal-transduction pathway mediated by human leukocyte interferon (IFN) in HeLa cells. IFN treatment results in a rapid increase in [3H]phorbol 12,13-dibutyrate binding to intact cells, indicating an activation of PKC. In addition, inhibitors of PKC (H7 and staurosporine) block the induction of antiviral activity by IFN against vesicular stomatitis virus. PKC inhibitors also block the accumulation of IFN-stimulated mRNAs in the cytoplasm of HeLa cells and suppress the transcriptional induction of IFN-stimulated genes. Activation of IFN-stimulated genes is mediated through a DNA response element that is necessary and sufficient for the transcriptional response to IFN. IFN treatment induces the appearance of several DNA-binding factors that specifically recognize the response element, and the appearance of these factors is suppressed by PKC inhibitors. This observation provides evidence that PKC activity is involved during IFN-stimulated signal transduction. Although activation of PKC appears to be required for the response to IFN, agonists of PKC activity alone do not turn on expression of IFN-stimulated genes.
Reich
N C
NC
Department of Pathology, State University of New York, Stony Brook 11794.
Pfeffer
L M
LM
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology; D015152:Blotting, Northern; D004268:DNA-Binding Proteins / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D006367:HeLa Cells; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins; D019311:Staurosporine; D014158:Transcription, Genetic / Q000187:drug effects; D014721:Vesicular stomatitis Indiana virus / Q000254:growth & development; D014779:Virus Replication / Q000187:drug effects
D000470:Alkaloids; D004268:DNA-Binding Proteins; D007370:Interferon Type I; D007546:Isoquinolines; D010879:Piperazines; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015240:Phorbol 12,13-Dibutyrate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C053177:N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide; D011493:Protein Kinase C; D019311:Staurosporine