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PMID: 7532278 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Role of STAT2 in the alpha interferon signaling pathway.

Molecular and cellular biology ·Vol. 15 ·No. 3 ·1995-03-00 ·Pages 1312-7

Leung S, Qureshi SA, Kerr IM, Darnell JE, Stark GR

Abstract

We have isolated U6A, a mutant cell line which lacks the STAT2 subunit of the transcription factor interferon (IFN)-stimulated gene factor 3 (ISGF3). The response of U6A cells to IFN-alpha is almost completely defective, but the response to IFN-gamma is normal. Complementation of U6A cells with a cDNA encoding STAT2 restores the IFN-alpha response, proving that STAT2 is required in this pathway. Binding of IFNs to their receptors triggers tyrosine phosphorylation and activation of the receptors, JAK family kinases, STAT1, and STAT2. In IFN-alpha-treated U6A cells, phosphorylation of the essential tyrosine kinases TYK2 and JAK1 is normal, but the phosphorylation of STAT1 is weak. A mutant STAT2 protein in which the phosphorylated tyrosine at position 690 is changed to phenylalanine does not restore normal phosphorylation of STAT1 in response to IFN-alpha. The dependence of STAT1 phosphorylation on the presence of STAT2 but not vice versa (T. Improta, C. Schindler, C. M. Horvath, I. M. Kerr, G. R. Stark, and J. E. Darnell, Jr., Proc. Natl. Acad. Sci. USA 91:4776-4780, 1994) indicates that in the formation of ISGF3, these two proteins may be phosphorylated sequentially in response to IFN-alpha and that phosphorylated STAT2 may be required to allow unphosphorylated STAT1 to bind to the activated IFN-alpha receptor.

MeSH Terms
Antibodies Antibodies, Monoclonal Cell Line DNA-Binding Proteins/genetics,physiology Genetic Complementation Test Humans Immunoblotting Interferon Type I/pharmacology Interferon-Stimulated Gene Factor 3 Interferon-Stimulated Gene Factor 3, gamma Subunit Interferon-beta/pharmacology Interferon-gamma/pharmacology Mutagenesis Phosphorylation Phosphotyrosine Protein Binding Recombinant Proteins/pharmacology Signal Transduction/drug effects,physiology Transcription Factors/genetics,physiology Transfection Tyrosine/analogs & derivatives,analysis
Chemicals
Antibodies Antibodies, Monoclonal DNA-Binding Proteins IRF9 protein, human Interferon Type I Interferon-Stimulated Gene Factor 3 Interferon-Stimulated Gene Factor 3, gamma Subunit Recombinant Proteins Transcription Factors Phosphotyrosine Tyrosine Interferon-beta Interferon-gamma
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Leung S
Department of Molecular Biology, Cleveland Clinic Foundation, Ohio 44195.
Qureshi S A
Kerr I M
Darnell J E
Stark G R
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.15.3.1312
Published
1995-03-00
Pages
1312-7
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC230354
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.15.3.1312 PMC Full Text View journal details
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