Evidence map›Paper›PMID 32929041›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2020

AKT Regulates NLRP3 Inflammasome Activation by Phosphorylating NLRP3 Serine 5.

Wei Zhao, Chong-Shan Shi, Kathleen Harrison, Il-Young Hwang, Neel R Nabar, Min Wang, John H Kehrl

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

Article in Journal of immunology (Baltimore, Md. : 1950), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 1 pooled it
3.4field-weighted citation impact, top 6% 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

51 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.

  1. Pooled it
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  5. Molecular mechanisms of NLRP3 inflammasome activation.Experimental & molecular medicine · 2026
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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

7 authors at 2 institutions in 2 countries.

Wei ZhaoDepartment of Prosthodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an 710004, China.
Chong-Shan ShiB Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Kathleen HarrisonB Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Il-Young HwangB Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Neel R NabarB Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.ORCID 0000-0002-9704-3570
Min WangState Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, China; and.
John H KehrlB Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; Jkehrl@niaid.nih.gov.ORCID 0000-0002-6526-159X
National Institutes of Health · USSichuan University · CN

Funding

SIGNAL TRANSDUCTION IN B LYMPHOCYTES: INDENTIFICATION OF KEY SIGNALING MOLECULEZ01AI000739 · NIAID · NIAID EXTRAMURAL ACTIVITIES · PI KEHRL, JOHN H · 1996 to 2008
$1.5M
Intramural NIH HHS Z01 AI000739
6 · The paper itself

Abstract

The cytosolic pattern recognition receptor NLRP3 senses host-derived danger signals and certain microbe-derived products in both humans and rodents. NLRP3 activation assembles an inflammasome complex that contains the adapter proteins ASC and caspase-1, whose activation triggers the maturation and release of the proinflammatory cytokines IL-1β and IL-18. S5 phosphorylation of NLRP3 prevents its oligomerization and activation, whereas dephosphorylation of this residue by the phosphatase PP2A allows NLRP3 activation. However, the protein kinase that mediates NLRP3 S5 phosphorylation is unknown. In this study, we show that AKT associates with NLRP3 and phosphorylates it on S5, limiting NLRP3 oligomerization. This phosphorylation event also stabilizes NLRP3 by reducing its ubiquitination on lysine 496, which inhibits its proteasome-mediated degradation by the E3 ligase Trim31. Pharmacologic manipulation of AKT kinase activity reciprocally modulates NLRP3 inflammasome-mediated IL-1β production. Inhibition of AKT reduced IL-1β production following the i.p. injection of LPS into mice. We propose that AKT, Trim31, and PP2A together modulate NLRP3 protein levels and the tendency to oligomerize, thereby setting a tightly regulated threshold for NLRP3 activation.

Indexed as

AnimalsCaspase 1InflammasomesInterleukin-18Interleukin-1betaMiceNLR Family, Pyrin Domain-Containing 3 ProteinPhosphorylationProteasome Endopeptidase ComplexProteolysisProto-Oncogene Proteins c-aktTripartite Motif ProteinsUbiquitinationUbiquitin-Protein LigasesCasp1 protein, mouseCaspase 1IL1B protein, mouseInflammasomesInterleukin-18Interleukin-1betaNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseProteasome Endopeptidase ComplexProto-Oncogene Proteins c-aktTRIM31 protein, mouseTripartite Motif ProteinsUbiquitin-Protein Ligases

Identifiers

PMID32929041
PMCPMC7541779
OpenAlexW3086462318

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.