Interferon-gamma-induced transcriptional activation is mediated by protein kinase C.
Interferon-gamma (IFN-gamma) regulates a variety of biological functions and is the principal lymphokine known to activate macrophages. In studies of the molecular mechanisms by which these cells are regulated by IFN-gamma, the transcriptional activation of an IFN-gamma-inducible gene, gamma.1, in human macrophage-like cell lines was examined. Transcription of this gene is rapidly induced by 0.1-1 unit of IFN-gamma. In addition, gamma.1 transcription is efficiently induced by phorbol 12-myristate 13-acetate, which is known to activate protein kinase C (PKC). Both stimulators of gamma.1 transcription induce the translocation of PKC from the cytosol of a membrane fraction. Two selective inhibitors of PKC, H7 and sphingosine, suppressed not only the induction of gamma.1 mRNA but transcription of HLA-DR by IFN-gamma as well. These findings establish that PKC plays a significant role in the signal transduction pathway leading to transcriptional activation of some IFN-gamma-regulated genes of cells of the mononuclear phagocyte lineage.
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D001692:Biological Transport; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D008264:Macrophages / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D013110:Sphingosine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic
D006684:HLA-DR Antigens; D007546:Isoquinolines; D010879:Piperazines; D012333:RNA, Messenger; D007371:Interferon-gamma; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate