Evidence map›Paper›PMID 10485875›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America1999

Inhibition of protein phosphatase 2A induces serine/threonine phosphorylation, subcellular redistribution, and functional inhibition of STAT3.

A Woetmann, M Nielsen, S T Christensen, J Brockdorff, K Kaltoft, A M Engel, S Skov, C Brender, C Geisler, A Svejgaard and 3 more

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
3.4field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

60 citing papers in PubMed, 134 citations in OpenAlex.

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  4. Protein Phosphatase 2A: Role in T Cells and Diseases.Journal of immunology research · 2023
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  14. Review
  15. Phosphatase PP2A is essential for TProceedings of the National Academy of Sciences of the United States of America · 2019
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 1 country.

A WoetmannInstitute of Medical Microbiology and Immunology, University of Copenhagen, DK2200 Copenhagen, Denmark.
M Nielsen
S T Christensen
J Brockdorff
K Kaltoft
A M Engel
S Skov
C Brender
C Geisler
A Svejgaard
J Rygaard
V Leick
N Odum
Aarhus University · DKUniversity of Copenhagen · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Signal transducers and activators of transcription (STATs) are rapidly phosphorylated on tyrosine residues in response to cytokine and growth factor stimulation of cell surface receptors. STATs hereafter are translocated to the nucleus where they act as transcription factors. Recent reports suggest that serine phosphorylation of STATs also is involved in the regulation of STAT-mediated gene transcription. Here, we studied the role of serine/threonine phosphatases in STAT3 signaling in human antigen-specific CD4(+) T cell lines and cutaneous T cell lymphoma lines, expressing a constitutively activated STAT3. We show that an inhibitor of protein phosphatases (PPs) PP1/PP2A, calyculin A, induces (i) phosphorylation of STAT3 on serine and threonine residues, (ii) inhibition of STAT3 tyrosine phosphorylation and DNA binding activity, and (iii) relocation of STAT3 from the nucleus to the cytoplasm. Similar results were obtained with other PP2A inhibitors (okadaic acid, endothall thioanhydride) but not with inhibitors of PP1 (tautomycin) or PP2B (cyclosporine A). Pretreatment with the broad serine/threonine kinase inhibitor staurosporine partly blocked the calyculin A-induced STAT3 phosphorylation, whereas inhibitors of serine/threonine kinases, such as mitogen-activated protein kinase-1 extracellular-regulated kinase-kinase, mitogen-activated protein p38 kinase, and phosphatidylinositol 3-kinase, did not. In conclusion, we provide evidence that PP2A plays a crucial role in the regulation of STAT3 phosphorylation and subcellular distribution in T cells. Moreover, our findings suggest that the level of STAT3 phosphorylation is balanced between a staurosporine-sensitive kinase(s) and PP2A.

Indexed as

Calcineurin InhibitorsCD4-Positive T-LymphocytesCell NucleusCyclosporineCytoplasmDNA-Binding ProteinsEnzyme InhibitorsHumansMarine ToxinsMicroscopy, ConfocalOxazolesPhosphoprotein PhosphatasesPhosphorylationProtein Phosphatase 2SerineSignal TransductionCalcineurin Inhibitorscalyculin ACyclosporineDNA-Binding ProteinsEnzyme InhibitorsMarine ToxinsOxazolesPhosphoprotein PhosphatasesProtein Phosphatase 2SerineSTAT3 protein, humanSTAT3 Transcription FactorStaurosporineThreonineTrans-Activators

Identifiers

PMID10485875
PMCPMC17932
OpenAlexW1998453743

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.