Home LiteratureArticle Details
PMID: 2174163 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Evidence for involvement of protein kinase C in the cellular response to interferon alpha.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 87 ·No. 22 ·1990-11-00 ·Pages 8761-5

Reich NC, Pfeffer LM

Abstract

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.

Related Genes
ISG15 ISG54
MeSH Terms
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine Alkaloids/pharmacology Blotting, Northern DNA-Binding Proteins/physiology Gene Expression/drug effects HeLa Cells In Vitro Techniques Interferon Type I/pharmacology Isoquinolines/pharmacology Phorbol 12,13-Dibutyrate/metabolism Piperazines/pharmacology Protein Kinase C/antagonists & inhibitors,physiology RNA, Messenger/genetics Recombinant Proteins Staurosporine Transcription, Genetic/drug effects Vesicular stomatitis Indiana virus/growth & development Virus Replication/drug effects
Chemicals
Alkaloids DNA-Binding Proteins Interferon Type I Isoquinolines Piperazines RNA, Messenger Recombinant Proteins Phorbol 12,13-Dibutyrate 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide Protein Kinase C Staurosporine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Reich N C
Department of Pathology, State University of New York, Stony Brook 11794.
Pfeffer L M
References (32)
32 references, click to expand
  1. Activation of the human beta-interferon gene requires an interferon-inducible factor.
    Mol Cell Biol. 1986 Mar;6(3):801-10 PMID: 3773893
  2. An early event in the interferon-induced transmembrane signaling process.
    Science. 1986 Oct 17;234(4774):355-8 PMID: 2429366
  3. Interferons and their actions.
    Annu Rev Biochem. 1987;56:727-77 PMID: 2441659
  4. Interferon-induced transcription of a gene encoding a 15-kDa protein depends on an upstream enhancer element.
    Proc Natl Acad Sci U S A. 1987 Sep;84(18):6394-8 PMID: 3476954
  5. Transcription of interferon-stimulated genes is induced by adenovirus particles but is suppressed by E1A gene products.
    J Virol. 1988 Jan;62(1):114-9 PMID: 2446013
  6. Increases in intracellular Ca2+ regulate the binding of [3H]phorbol 12,13-dibutyrate to intact 1321N1 astrocytoma cells.
    J Biol Chem. 1989 Feb 25;264(6):3102-7 PMID: 2783692
  7. Phorbol ester-mediated down-regulation of an interferon-inducible gene.
    J Biol Chem. 1989 Feb 25;264(6):3252-5 PMID: 2464596
  8. Rapid activation by interferon alpha of a latent DNA-binding protein present in the cytoplasm of untreated cells.
    Proc Natl Acad Sci U S A. 1989 Feb;86(4):1203-7 PMID: 2919169
  9. Signal transduction pathways in the induction of 2',5'-oligoadenylate synthetase gene expression by interferon alpha/beta.
    Proc Natl Acad Sci U S A. 1989 Apr;86(7):2243-7 PMID: 2538838
  10. Overlapping sites for constitutive and induced DNA binding factors involved in interferon-stimulated transcription.
    EMBO J. 1989 Mar;8(3):831-9 PMID: 2721502
  11. Differential binding of interferon-induced factors to an oligonucleotide that mediates transcriptional activation.
    Nucleic Acids Res. 1989 May 11;17(9):3415-24 PMID: 2726484
  12. A functional protein kinase C is required for induction of 2-5A synthetase by recombinant interferon-alpha A in Daudi cells.
    J Biol Chem. 1989 Aug 25;264(24):14305-11 PMID: 2474543
  13. 2-Aminopurine selectively blocks the transcriptional activation of cellular genes by virus, double-stranded RNA and interferons in human cells.
    Eur J Biochem. 1989 Oct 1;184(3):503-9 PMID: 2478362
  14. Alpha interferon and gamma interferon stimulate transcription of a single gene through different signal transduction pathways.
    Mol Cell Biol. 1989 Dec;9(12):5404-11 PMID: 2555698
  15. Cytoplasmic activation of ISGF3, the positive regulator of interferon-alpha-stimulated transcription, reconstituted in vitro.
    Genes Dev. 1989 Sep;3(9):1362-71 PMID: 2606351
  16. Purification and cloning of interferon-stimulated gene factor 2 (ISGF2): ISGF2 (IRF-1) can bind to the promoters of both beta interferon- and interferon-stimulated genes but is not a primary transcriptional activator of either.
    Mol Cell Biol. 1990 Jun;10(6):2448-57 PMID: 2342456
  17. Interferon-alpha selectively activates the beta isoform of protein kinase C through phosphatidylcholine hydrolysis.
    Proc Natl Acad Sci U S A. 1990 Sep;87(17):6537-41 PMID: 2168551
  18. Down-regulation of protein kinase C is due to an increased rate of degradation.
    Biochem J. 1987 Jun 15;244(3):775-9 PMID: 3446191
  19. Interferon response element of the human gene 6-16.
    EMBO J. 1988 Jan;7(1):85-92 PMID: 3359997
  20. Interferon-induced nuclear factors that bind a shared promoter element correlate with positive and negative transcriptional control.
    Genes Dev. 1988 Apr;2(4):383-93 PMID: 3371658
  21. Interferon-induced binding of nuclear factors to promoter elements of the 2-5A synthetase gene.
    EMBO J. 1988 Mar;7(3):751-9 PMID: 2456211
  22. Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements.
    Cell. 1988 Sep 9;54(6):903-13 PMID: 3409321
  23. Enhancer-like interferon responsive sequences of the human and murine (2'-5') oligoadenylate synthetase gene promoters.
    EMBO J. 1988 May;7(5):1411-9 PMID: 2457496
  24. Gene induction by interferons and double-stranded RNA: selective inhibition by 2-aminopurine.
    Mol Cell Biol. 1988 Oct;8(10):4289-94 PMID: 2460741
  25. Biochemistry of interferons and their actions.
    Annu Rev Biochem. 1982;51:251-82 PMID: 6180680
  26. Transcriptional induction of two genes in human cells by beta interferon.
    Proc Natl Acad Sci U S A. 1984 Nov;81(21):6733-7 PMID: 6436820
  27. Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide dependent protein kinase and protein kinase C.
    Biochemistry. 1984 Oct 9;23(21):5036-41 PMID: 6238627
  28. Transcriptional induction by interferon. New protein(s) determine the extent and length of the induction.
    J Biol Chem. 1986 Jan 5;261(1):453-9 PMID: 2934388
  29. Cytosolic calcium regulates phorbol diester binding affinity in intact phagocytes.
    J Biol Chem. 1986 Mar 25;261(9):4097-100 PMID: 3081515
  30. Staurosporine, a potent inhibitor of phospholipid/Ca++dependent protein kinase.
    Biochem Biophys Res Commun. 1986 Mar 13;135(2):397-402 PMID: 3457562
  31. Studies and perspectives of protein kinase C.
    Science. 1986 Jul 18;233(4761):305-12 PMID: 3014651
  32. Interferon-stimulated transcription: isolation of an inducible gene and identification of its regulatory region.
    Proc Natl Acad Sci U S A. 1986 Dec;83(23):8929-33 PMID: 3466167
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.87.22.8761
Published
1990-11-00
Pages
8761-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC55039
Subset
IM
Grants
NCI NIH HHS · CA 50773 · United States
NIGMS NIH HHS · GM 36716 · United States
External Links
PubMed source DOI: 10.1073/pnas.87.22.8761 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2