Evidence map›Paper›PMID 23023391›Full record

ArticleNature immunology2012

The p110δ isoform of the kinase PI(3)K controls the subcellular compartmentalization of TLR4 signaling and protects from endotoxic shock.

Ezra Aksoy, Salma Taboubi, David Torres, Sandrine Delbauve, Abderrahman Hachani, Maria A Whitehead, Wayne P Pearce, Inma M Berenjeno, Gemma Nock, Alain Filloux and 3 more

Erratum issuedOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature immunology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 119 papers.

0numbers the graph read from it
0cells of the map it votes in
119citing papers in PubMed
6.6field-weighted citation impact, top 3% 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

119 citing papers in PubMed, 186 citations in OpenAlex.

  1. Trial
  2. Review
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  4. From the gene to the clinic: Key milestones in the PI3Kδ journey.Journal of immunology (Baltimore, Md. : 1950) · 2026
    Review
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  17. Ergosterol Isolated fromMolecules (Basel, Switzerland) · 2023
    Article
  18. Article
  19. Article
  20. Article

59 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 2 countries.

Ezra AksoyCentre for Cell Signaling, Barts Institute of Cancer, Queen Mary, University of London, London, UK.
Salma TaboubiCentre for Cell Signaling, Barts Institute of Cancer, Queen Mary, University of London, London, UK.
David Torres *Institute for Medical Immunology, Free University of Brussels, Gosselies, Belgium.
Sandrine Delbauve *Institute for Medical Immunology, Free University of Brussels, Gosselies, Belgium.
Abderrahman HachaniDivision of Cell and Molecular Biology, Centre for Molecular Microbiology and Infection, Imperial College London, London, UK.
Maria A WhiteheadCentre for Cell Signaling, Barts Institute of Cancer, Queen Mary, University of London, London, UK.
Wayne P PearceCentre for Cell Signaling, Barts Institute of Cancer, Queen Mary, University of London, London, UK.
Inma M BerenjenoCentre for Cell Signaling, Barts Institute of Cancer, Queen Mary, University of London, London, UK.
Gemma NockCentre for Cell Signaling, Barts Institute of Cancer, Queen Mary, University of London, London, UK.
Alain FillouxDivision of Cell and Molecular Biology, Centre for Molecular Microbiology and Infection, Imperial College London, London, UK.
Rudi BeyaertDepartment for Molecular Biomedical Research, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent, Belgium.
Veronique FlamandInstitute for Medical Immunology, Free University of Brussels, Gosselies, Belgium.
Bart VanhaesebroeckCentre for Cell Signaling, Barts Institute of Cancer, Queen Mary, University of London, London, UK.
Queen Mary University of London · GBImperial College London · GBVIB-UGent Center for Inflammation Research · BE

Funding

Cancer Research UK C23338/A10200Wellcome Trust 091939
6 · The paper itself

Abstract

Lipopolysaccharide activates plasma-membrane signaling and endosomal signaling by Toll-like receptor 4 (TLR4) through the TIRAP-MyD88 and TRAM-TRIF adaptor complexes, respectively, but it is unclear how the signaling switch between these cell compartments is coordinated. In dendritic cells, we found that the p110δ isoform of phosphatidylinositol-3-OH kinase (PI(3)K) induced internalization of TLR4 and dissociation of TIRAP from the plasma membrane, followed by calpain-mediated degradation of TIRAP. Accordingly, inactivation of p110δ prolonged TIRAP-mediated signaling from the plasma membrane, which augmented proinflammatory cytokine production while decreasing TRAM-dependent endosomal signaling that generated anti-inflammatory cytokines (interleukin 10 and interferon-β). In line with that altered signaling output, p110δ-deficient mice showed enhanced endotoxin-induced death. Thus, by controlling the 'topology' of TLR4 signaling complexes, p110δ balances overall homeostasis in the TLR4 pathway.

Indexed as

AnimalsCalpainCell CompartmentationCell MembraneCells, CulturedClass Ia Phosphatidylinositol 3-KinaseDendritic CellsEndosomesGene ExpressionInterferon-betaInterleukin-10IsoenzymesLipopolysaccharidesMembrane GlycoproteinsMiceMice, KnockoutCalpainClass Ia Phosphatidylinositol 3-KinaseInterferon-betaInterleukin-10IsoenzymesLipopolysaccharidesMembrane GlycoproteinsReceptors, InterleukinReceptors, Interleukin-1Ticam2 protein, mouseTIRAP protein, mouseTlr4 protein, mouseToll-Like Receptor 4

Identifiers

PMID23023391
PMCPMC4018573
OpenAlexW2015665561

What OpenQuestion holds

Textmetadata
LicenceTDM
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.