Evidence map›Paper›PMID 28130450›Full record

ArticleThe Journal of biological chemistry2017

Small GTPase Rab8a-recruited Phosphatidylinositol 3-Kinase γ Regulates Signaling and Cytokine Outputs from Endosomal Toll-like Receptors.

Adam A Wall, Lin Luo, Yu Hung, Samuel J Tong, Nicholas D Condon, Antje Blumenthal, Matthew J Sweet, Jennifer L Stow

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

47 citing papers in PubMed, 75 citations in OpenAlex.

  1. The Manipulation of Host Cells byInternational journal of molecular sciences · 2026
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  6. Targeting PI3Kγ in cancer.Trends in cancer · 2025
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  7. The interplay betweenCell insight · 2025
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  11. Tropical medicine and infectious disease · 2023
    Review
  12. Speaking the host language: howMicrobiology (Reading, England) · 2023
    Review
  13. Article
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  15. Genomic Survey ofPlants (Basel, Switzerland) · 2022
    Article
  16. Article
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  19. Article
  20. Maximizing insights from monogenic immune disorders.Current opinion in immunology · 2021
    Review
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

8 authors at 1 institution in 1 country.

Adam A WallFrom the Institute for Molecular Bioscience (IMB) and IMB Centre for Inflammation and Disease Research, University of Queensland, Brisbane, Queensland 4072, Australia and.
Lin LuoFrom the Institute for Molecular Bioscience (IMB) and IMB Centre for Inflammation and Disease Research, University of Queensland, Brisbane, Queensland 4072, Australia and.
Yu HungFrom the Institute for Molecular Bioscience (IMB) and IMB Centre for Inflammation and Disease Research, University of Queensland, Brisbane, Queensland 4072, Australia and.
Samuel J TongFrom the Institute for Molecular Bioscience (IMB) and IMB Centre for Inflammation and Disease Research, University of Queensland, Brisbane, Queensland 4072, Australia and.
Nicholas D CondonFrom the Institute for Molecular Bioscience (IMB) and IMB Centre for Inflammation and Disease Research, University of Queensland, Brisbane, Queensland 4072, Australia and.
Antje Blumenthalthe University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, Queensland 4102, Australia.
Matthew J SweetFrom the Institute for Molecular Bioscience (IMB) and IMB Centre for Inflammation and Disease Research, University of Queensland, Brisbane, Queensland 4072, Australia and.
Jennifer L StowFrom the Institute for Molecular Bioscience (IMB) and IMB Centre for Inflammation and Disease Research, University of Queensland, Brisbane, Queensland 4072, Australia and j.stow@imb.uq.edu.au.
University of Queensland · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

LPS-mediated activation of Toll-like receptor 4 (TLR4) in macrophages results in the coordinated release of proinflammatory cytokines, followed by regulatory mediators, to ensure that this potentially destructive pathway is tightly regulated. We showed previously that Rab8a recruits PI3Kγ for Akt-dependent signaling during TLR4 activation to limit the production of the proinflammatory cytokines IL-6 and IL-12p40 while enhancing the release of the regulatory/anti-inflammatory cytokine IL-10. Here we broaden the array of immune receptors controlled by Rab8a-PI3Kγ and further define the Rab-mediated membrane domains required for signaling. With CRISPR/Cas9-mediated gene editing to stably knock out and recover Rab8a in macrophage cell lines, we match Akt signaling profiles with cytokine outputs, confirming that Rab8a is a novel regulator of the Akt/mammalian target of rapamycin (mTOR) pathway downstream of multiple TLRs. Upon developing a Rab8a activation assay, we show that TLR3 and 9 agonists also activate Rab8a. Live-cell imaging reveals that Rab8a is first recruited to the plasma membrane and dorsal ruffles, but it is retained during collapse of ruffles to form macropinosomes enriched for phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P

Indexed as

AnimalsCells, CulturedClass Ib Phosphatidylinositol 3-KinaseCytokinesFemaleHumansMacrophagesMaleMiceMice, Inbred C57BLPhosphatidylinositol Phosphatesrab GTP-Binding ProteinsRAW 264.7 CellsSignal TransductionToll-Like ReceptorsClass Ib Phosphatidylinositol 3-KinaseCytokinesphosphatidylinositol 3,4,5-triphosphatephosphatidylinositol 3,4-diphosphatePhosphatidylinositol PhosphatesPik3cg protein, mouseRab8a protein, mouserab GTP-Binding ProteinsToll-Like ReceptorsAkt PKBinflammationinnate immunitymacrophagemacropinocytosismammalian target of rapamycin (mTOR)PI3KRabRab8Toll-like receptor (TLR)

Identifiers

PMID28130450
PMCPMC5377761
OpenAlexW2580522110

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.