Home LiteratureArticle Details
PMID: 1280824 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Tyrosine phosphorylation is required for activation of an alpha interferon-stimulated transcription factor.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 89 ·No. 23 ·1992-12-01 ·Pages 11411-5

Gutch MJ, Daly C, Reich NC

Abstract

The signal transduction pathway of alpha interferon utilizes tyrosine phosphorylation to transmit a signal generated at the cell surface to the transcriptional machinery in the nucleus. Activation of the interferon pathway initiates with the binding of alpha interferon to its cell surface receptor. The ligand-receptor complex signals the activation of a latent cytoplasmic transcription factor. The active form of the interferon-stimulated gene factor (ISGF3) is phosphorylated on tyrosine residues. ISGF3 subsequently translocates to the nucleus and binds to a DNA sequence, the interferon-stimulated response element, found within the promoter of inducible genes. ISGF3 is a multicomponent factor consisting of four proteins of 113 kDa, 91 kDa, 84 kDa, and 48 kDa. Three proteins consistent with sizes of 113 kDa, 91 kDa, and 84 kDa copurify with ISGF3 and are phosphorylated on tyrosine residues after stimulation by alpha interferon. Tyrosine phosphorylation is essential for activation of ISGF3. Genistein, a tyrosine kinase inhibitor, blocks the appearance of ISGF3 and blocks the transcriptional stimulation of interferon-induced genes. This study shows that tyrosine phosphorylation provides a link between the interferon-receptor complex at the plasma membrane and specific activation of gene expression in the nucleus.

MeSH Terms
Base Sequence DNA-Binding Proteins/chemistry,metabolism HeLa Cells Humans In Vitro Techniques Interferon-Stimulated Gene Factor 3 Interferon-Stimulated Gene Factor 3, gamma Subunit Interferon-alpha/pharmacology Molecular Sequence Data Molecular Weight Oligodeoxyribonucleotides/chemistry Phosphorylation Phosphotyrosine Protein-Tyrosine Kinases/metabolism Receptors, Interferon/physiology Regulatory Sequences, Nucleic Acid Signal Transduction Transcription Factors/chemistry,metabolism Transcription, Genetic Tyrosine/analogs & derivatives,metabolism
Chemicals
DNA-Binding Proteins IRF9 protein, human Interferon-Stimulated Gene Factor 3 Interferon-Stimulated Gene Factor 3, gamma Subunit Interferon-alpha Oligodeoxyribonucleotides Receptors, Interferon Transcription Factors Phosphotyrosine Tyrosine Protein-Tyrosine Kinases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Gutch M J
Department of Pathology, State University of New York, Stony Brook 11794.
Daly C
Reich N C
References (34)
34 references, click to expand
  1. The interferon system. A bird's eye view of its biochemistry.
    J Biol Chem. 1992 Mar 15;267(8):5017-20 PMID: 1371992
  2. 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
  3. Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor.
    Science. 1992 Aug 7;257(5071):809-13 PMID: 1496401
  4. Role of protein phosphorylation in activation of interferon-stimulated gene factors.
    J Biol Chem. 1992 Mar 25;267(9):6389-95 PMID: 1556141
  5. A transcription factor with SH2 and SH3 domains is directly activated by an interferon alpha-induced cytoplasmic protein tyrosine kinase(s).
    Cell. 1992 Jul 24;70(2):323-35 PMID: 1638633
  6. SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins.
    Science. 1991 May 3;252(5006):668-74 PMID: 1708916
  7. The control of interferon-inducible gene expression.
    FEBS Lett. 1991 Jul 22;285(2):194-8 PMID: 1713174
  8. Transcriptional regulation of interferon-stimulated genes.
    Eur J Biochem. 1991 Aug 15;200(1):1-11 PMID: 1715271
  9. Signal transduction by the SRC family of tyrosine protein kinases in hemopoietic cells.
    Cell Growth Differ. 1991 Aug;2(8):409-14 PMID: 1724382
  10. Protein kinase activity required for an early step in interferon-alpha signaling.
    J Biol Chem. 1991 Dec 5;266(34):23471-6 PMID: 1744140
  11. Transmembrane signaling by interferon alpha involves diacylglycerol production and activation of the epsilon isoform of protein kinase C in Daudi cells.
    Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):7988-92 PMID: 1832772
  12. Oncogenes and signal transduction.
    Cell. 1991 Jan 25;64(2):281-302 PMID: 1846320
  13. Signal transduction by interferon-alpha through arachidonic acid metabolism.
    Science. 1991 Jan 11;251(4990):204-7 PMID: 1898993
  14. Synergistic interaction between interferon-alpha and interferon-gamma through induced synthesis of one subunit of the transcription factor ISGF3.
    EMBO J. 1990 Apr;9(4):1105-11 PMID: 2108862
  15. Characterization of three monoclonal antibodies that recognize the interferon alpha 2 receptor.
    Proc Natl Acad Sci U S A. 1990 Sep;87(18):7230-4 PMID: 2144902
  16. Genetic transfer of a functional human interferon alpha receptor into mouse cells: cloning and expression of its cDNA.
    Cell. 1990 Jan 26;60(2):225-34 PMID: 2153461
  17. Signal transduction by receptors with tyrosine kinase activity.
    Cell. 1990 Apr 20;61(2):203-12 PMID: 2158859
  18. Evidence for involvement of protein kinase C in the cellular response to interferon alpha.
    Proc Natl Acad Sci U S A. 1990 Nov;87(22):8761-5 PMID: 2174163
  19. ISGF3, the transcriptional activator induced by interferon alpha, consists of multiple interacting polypeptide chains.
    Proc Natl Acad Sci U S A. 1990 Nov;87(21):8555-9 PMID: 2236065
  20. Interferon-alpha regulates nuclear translocation and DNA-binding affinity of ISGF3, a multimeric transcriptional activator.
    Genes Dev. 1990 Oct;4(10):1753-65 PMID: 2249773
  21. Interferons and their actions.
    Annu Rev Biochem. 1987;56:727-77 PMID: 2441659
  22. 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
  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. Phospholipase C-gamma is a substrate for the PDGF and EGF receptor protein-tyrosine kinases in vivo and in vitro.
    Cell. 1989 Jun 30;57(7):1109-22 PMID: 2472219
  25. A single DNA response element can confer inducibility by both alpha- and gamma-interferons.
    Proc Natl Acad Sci U S A. 1989 Feb;86(3):840-4 PMID: 2492664
  26. Use of a selectable marker regulated by alpha interferon to obtain mutations in the signaling pathway.
    Mol Cell Biol. 1989 Nov;9(11):4605-12 PMID: 2513475
  27. 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
  28. 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
  29. 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
  30. Genistein, a specific inhibitor of tyrosine-specific protein kinases.
    J Biol Chem. 1987 Apr 25;262(12):5592-5 PMID: 3106339
  31. Interferon response element of the human gene 6-16.
    EMBO J. 1988 Jan;7(1):85-92 PMID: 3359997
  32. 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
  33. Affinity purification of sequence-specific DNA binding proteins.
    Proc Natl Acad Sci U S A. 1986 Aug;83(16):5889-93 PMID: 3461465
  34. A protein tyrosine kinase in the interferon alpha/beta signaling pathway.
    Cell. 1992 Jul 24;70(2):313-22 PMID: 1386289
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.89.23.11411
Published
1992-12-01
Pages
11411-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC50560
Subset
IM
Grants
NCI NIH HHS · R29CA 50773 · United States
External Links
PubMed source DOI: 10.1073/pnas.89.23.11411 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: product@genelibs.com

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