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The rapid inactivation of nuclear tyrosine phosphorylated Stat1 depends upon a protein tyrosine phosphatase.
Open accessAbstract
After interferon-gamma (IFN-gamma) treatment of cells the appearance of tyrosine phosphorylated Stat1 in the nucleus was maximal within 20-30 min, remained for 2-2.5 h and activated molecules disappeared by 4 h. In the absence of continued signaling from the receptor (imposed by staurosporine treatment) previously activated Stat1 disappeared completely within 60 min, implying continuous generation and removal of active molecules during extended IFN-gamma treatment. Proteasome inhibitors prolonged the time of activation of Stat1 by prolonging signaling from the receptor but not by blocking removal of already activated Stat1 molecules. By analyzing with 35S labeling the distribution of total Stat1 and activated Stat1, we concluded that the Stat1 molecules promptly cycle into the nucleus as tyrosine phosphorylated molecules and later return quantitatively to the cytoplasm as non-phosphorylated molecules. Therefore, the removal of the activated Stat1 molecules from the nucleus appears not to be proteolytic but must depend on a protein tyrosine phosphatase(s).
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“Given that Stat1 has a slow turnover time (t 1/2 > 8 h; Lee et al. 1997) but dephosphorylation is rapid (t 1/2 < 15 min; Haspel et al. 1996), we wanted to determine how long Stat1 molecules remained nuclear.”
From DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 (2003) · cites this paper as Haspel et al. 1996
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Metadata
- Authors
- Haspel, R. L., Salditt‐Georgieff, M., & Darnell, J. E.
- Affiliations
- Rockefeller University (US)
- ORCID
- Haspel, R. L.
- Venue
- The EMBO Journal
- Published
- 1996-11-01
- Volume
- 15
- Issue
- 22
- Pages
- 6262-6268
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC452449
- OpenAlex
- W1702674772
- Cited by
- 312
- References
- 41
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 1 · 2022: 1 · 2021: 5 · 2020: 1 · 2019: 2 · 2018: 4 · 2017: 1 · 2016: 3 · 2015: 4 · 2014: 12 · 2013: 9 · 2012: 6
- FWCI
- 12.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (GM07739)
- National Institute of Allergy and Infectious Diseases (R01AI032489, AI32489, AI324420)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- STAT1, tyrosine phosphorylation, protein tyrosine phosphatase, interferon-gamma signaling, nuclear translocation, proteasome inhibitors, staurosporine, receptor signaling, transcription factor regulation
- MeSH terms
- Acetylcysteine, Cell Nucleus, Cysteine Endopeptidases, DNA-Binding Proteins, Electrophoresis, Polyacrylamide Gel, Enzyme Inhibitors, Fibroblasts, Humans, Interferon-gamma, Leupeptins, Multienzyme Complexes, Nuclear Proteins, Phosphorylation, Vanadates, Blotting, Western, Signal Transduction, Trans-Activators, Protein Tyrosine Phosphatases, Receptors, Interferon, Phosphotyrosine, Staurosporine, Proteasome Endopeptidase Complex, STAT1 Transcription Factor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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