ArticleMolecular biology of the cell2007
A Mutation in the SH2 domain of STAT2 prolongs tyrosine phosphorylation of STAT1 and promotes type I IFN-induced apoptosis.
Article in Molecular biology of the cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Sarbecoviruses Suppress Innate Immunity by Recruiting PPM1A to Modulate STAT2 and ORF9b Phosphorylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Immunotherapeutic implications of negative regulation by protein tyrosine phosphatases in T cells: the emerging cases of PTP1B and TCPTP.Frontiers in medicine · 2024Review
- Extracellular microparticles derived from hepatic progenitor cells deliver a death signal to hepatoma-initiating cells.Journal of nanobiotechnology · 2022Article
- Engineering Chlamydomonas reinhardtii for Expression of Functionally Active Human Interferon-α.Molecular biotechnology · 2019Article
- Article
- Responses to Cytokines and Interferons that Depend upon JAKs and STATs.Cold Spring Harbor perspectives in biology · 2018Review
- TYK2-induced phosphorylation of Y640 suppresses STAT3 transcriptional activity.Scientific reports · 2017Article
- The past, present and future of immunotherapy against tumor.Translational lung cancer research · 2015Review
- Protein tyrosine phosphatases as wardens of STAT signaling.JAK-STAT · 2014Review
- STAT2 phosphorylation and signaling.JAK-STAT · 2013Review
- Wedelolactone, a naturally occurring coumestan, enhances interferon-γ signaling through inhibiting STAT1 protein dephosphorylation.The Journal of biological chemistry · 2013Article
- Interferons as inducers of apoptosis in malignant cells.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2013Review
- Immunomodulatory effects of interferons in malignancies.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2013Review
- Identification of STAT2 serine 287 as a novel regulatory phosphorylation site in type I interferon-induced cellular responses.The Journal of biological chemistry · 2013Article
- STAT2: A shape-shifting anti-viral super STAT.JAK-STAT · 2013Review
- Somatic STAT3 mutations in large granular lymphocytic leukemia.The New England journal of medicine · 2012Article
- The role of signal transducer and activator of transcription-2 in the interferon response.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2012Review
- Somatic mutations activating STAT3 in human inflammatory hepatocellular adenomas.The Journal of experimental medicine · 2011Article
- Resistance to IFN-alpha-induced apoptosis is linked to a loss of STAT2.Molecular cancer research : MCR · 2010Article
- Regulation of apoptosis by type III interferons.Cell proliferation · 2008Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Type I interferons (IFN-alpha/beta) induce apoptosis in certain tumor cell lines but not others. Here we describe a mutation in STAT2 that confers an apoptotic effect in tumor cells in response to type I IFNs. This mutation was introduced in a conserved motif, PYTK, located in the STAT SH2 domain, which is shared by STAT1, STAT2, and STAT3. To test whether the tyrosine in this motif might be phosphorylated and affect signaling, Y631 of STAT2 was mutated to phenylalanine (Y631F). Although it was determined that Y631 was not phosphorylated, the Y631F mutation conferred sustained signaling and induction of IFN-stimulated genes. This prolonged IFN response was associated with sustained tyrosine phosphorylation of STAT1 and STAT2 and their mutual association as heterodimers, which resulted from resistance to dephosphorylation by the nuclear tyrosine phosphatase TcPTP. Finally, cells bearing the Y631F mutation in STAT2 underwent apoptosis after IFN-alpha stimulation compared with wild-type STAT2. Therefore, this mutation reveals that a prolonged response to IFN-alpha could account for one difference between tumor cell lines that undergo IFN-alpha-induced apoptosis compared with those that display an antiproliferative response but do not die.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.