A Single Phosphotyrosine Residue of Stat91 Required for Gene Activation by Interferon-γ
Abstract
Interferon-γ (IFN-γ) stimulates transcription of specific genes by inducing tyrosine phosphorylation of a 91-kilodalton cytoplasmic protein (termed STAT for signal transducer and activator of transcription). Stat91 was phosphorylated on a single site (Tyr 701 ), and phosphorylation of this site was required for nuclear translocation, DNA binding, and gene activation. Stat84, a differentially spliced product of the same gene that lacks the 38 carboxyl-terminal amino acids of Stat91, did not activate transcription, although it was phosphorylated and translocated to the nucleus and bound DNA. Thus, Stat91 mediates activation of transcription in response to IFN-γ.
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Both IFNγ and IL-6 can activate JAK1 and JAK2, and subsequently STAT1 and STAT3.
“Both IFN␥ and IL-6 can activate JAK1 (4 -6) and JAK2 (7-10), and subsequently STAT1 (11,12) and STAT3 (6,13,14).”
From The Comparative Roles of Suppressor of Cytokine Signaling-1 and -3 in the Inhibition and Desensitization of Cytokine Signaling (2006) · cites this paper as [11]
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- Authors
- Shuai, K., Stark, G. R., Kerr, L. M., & Darnell, J. E.
- Affiliations
- Rockefeller University (US)
- Cleveland Clinic (US)
- Imperial Cancer Research Foundation, Lincoln's Inn Fields, London, United Kingdom.
- Rockefeller University, Laboratory of Molecular Cell Biology, New York, NY 10021.
- Venue
- Science
- Published
- 1993-09-24
- Volume
- 261
- Issue
- 5129
- Pages
- 1744-1746
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2041187882
- Cited by
- 802
- References
- 0
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 9 · 2023: 12 · 2022: 12 · 2021: 8 · 2020: 11 · 2019: 8 · 2018: 13 · 2017: 10 · 2016: 14 · 2015: 8 · 2014: 13 · 2013: 22 · 2012: 25
- FWCI
- 33.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI032489, AI32489-02)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Keywords
- interferon-gamma, signal transducer and activator of transcription, tyrosine phosphorylation, transcriptional activation, nuclear translocation, DNA binding, alternative splicing, gene expression regulation
- MeSH terms
- Amino Acid Sequence, Cell Line, Cell Nucleus, DNA-Binding Proteins, Gene Expression Regulation, Humans, Interferon-gamma, Molecular Sequence Data, Peptide Fragments, Transcription Factors, Transfection, Tyrosine, Signal Transduction, Transcriptional Activation, Phosphotyrosine
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