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Cited by 507Protein Tyrosine PhosphatasesCytokine Signaling Pathways and Interactionsinterferon and immune responses

Identification of a Nuclear Stat1 Protein Tyrosine Phosphatase

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ten Hoeve, Johanna, de Jesus Ibarra-Sanchez, Maria, Fu, Yubin, Zhu, Wei, Tremblay, Michel, David, Michael, Shuai, Ke·2002·Molecular and Cellular Biology
DOI 10.1128/mcb.22.16.5662-5668.2002PMC PMC133976
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Abstract

Upon interferon (IFN) stimulation, Stat1 becomes tyrosine phosphorylated and translocates into the nucleus, where it binds to DNA to activate transcription. The activity of Stat1 is dependent on tyrosine phosphorylation, and its inactivation in the nucleus is accomplished by a previously unknown protein tyrosine phosphatase (PTP). We have now purified a Stat1 PTP activity from HeLa cell nuclear extract and identified it as TC45, the nuclear isoform of the T-cell PTP (TC-PTP). TC45 can dephosphorylate Stat1 both in vitro and in vivo. Nuclear extracts lacking TC45 fail to dephosphorylate Stat1. Furthermore, the dephosphorylation of IFN-induced tyrosine-phosphorylated Stat1 is defective in TC-PTP-null mouse embryonic fibroblasts (MEFs) and primary thymocytes. Reconstitution of TC-PTP-null MEFs with TC45, but not the endoplasmic reticulum (ER)-associated isoform TC48, rescues the defect in Stat1 dephosphorylation. The dephosphorylation of Stat3, but not Stat5 or Stat6, is also affected in TC-PTP-null cells. Our results identify TC45 as a PTP responsible for the dephosphorylation of Stat1 in the nucleus.

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  • TC45 is a ubiquitously expressed Stat1-specific nuclear tyrosine phosphatase.

    “purified TC-PTPa (also called TC45; Ibarra-Sanchez et al. 2000), a ubiquitously expressed Stat1-specific nuclear tyrosine phosphatase (ten Hoeve et al. 2002).”

    From DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 (2003) · cites this paper as ten Hoeve et al. 2002

    The Results identify TC45 as a mainly nuclear phosphatase that dephosphorylates Stat1. But the Discussion says the TC-PTP gene is ubiquitously expressed—not specifically that TC45 is—and the Results and Discussion also implicate TC45 in Stat3 dephosphorylation, so “Stat1-specific” overstates its selectivity. Page numbers were not available in our copy. (LLM, conf=0.88)

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Authors
ten Hoeve, J., de Jesus Ibarra-Sanchez, M., Fu, Y., Zhu, W., Tremblay, M., David, M., & Shuai, K.
Affiliations
  • Department of Medicine
  • McGill Cancer Centre and Department of Biochemistry, McGill University, Montreal, Quebec H3G 1Y6, Canada
  • University of California San Diego (US)
  • McGill University (CA)
  • University of California, Los Angeles (US)
ORCID
Venue
Molecular and Cellular Biology
Publisher
Informa UK Limited
Published
2002-08-01
Volume
22
Issue
16
Pages
5662-5668
ISSN
  • 0270-7306 (ISSN-L)
  • 1098-5549
DOI
10.1128/mcb.22.16.5662-5668.2002
PMC
PMC133976
OpenAlex
W2147511779
Cited by
507
References
3
Citations by year
2026: 12 · 2025: 19 · 2024: 12 · 2023: 15 · 2022: 22 · 2021: 12 · 2020: 17 · 2019: 23 · 2018: 12 · 2017: 15 · 2016: 13 · 2015: 13 · 2014: 22 · 2013: 31 · 2012: 26
FWCI
11.39
Type
journal article
Language
en
Open access
Licence
journals.asm.org/non-commercial-tdm-license (tdm)
Locations
  • Molecular and Cellular Biology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Cancer Research Institute
  • National Institutes of Health
  • National Cancer Institute (R01CA080105, CA 80105)
  • National Institute of Allergy and Infectious Diseases (AI 43438, R01AI043438, R21AI043438)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Keywords
STAT1, protein tyrosine phosphatase, TCPTP, interferon signaling, STAT3, STAT5, STAT6, thymocytes, mouse embryonic fibroblasts, transcriptional regulation
MeSH terms
Animals, Cell Fractionation, Cell Line, DNA-Binding Proteins, Enzyme Inhibitors, Fibroblasts, Humans, Interferon-gamma, Interleukin-2, Isoenzymes, Nuclear Proteins, Phosphorylation, T-Lymphocytes, Thymus Gland, Signal Transduction, Trans-Activators, Protein Tyrosine Phosphatases, Staurosporine, STAT1 Transcription Factor, Mice, Protein Tyrosine Phosphatase, Non-Receptor Type 2

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