ArticleThe Biochemical journal2007
Cross-talk between IRAK-4 and the NADPH oxidase.
Article in The Biochemical journal, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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
33 citing papers in PubMed, 70 citations in OpenAlex.
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- Distinct Cell-specific Roles of NOX2 and MyD88 in Epileptogenesis.Frontiers in cell and developmental biology · 2022Review
- Crosstalk Between the Oxidative Stress and Glia Cells After Stroke: From Mechanism to Therapies.Frontiers in immunology · 2022Review
- SLAMF8 Downregulates Mouse Macrophage Microbicidal MechanismsFrontiers in immunology · 2022Article
- Transcriptomic Analysis Reveal the Molecular Mechanisms of Seed Coat Development inFrontiers in plant science · 2022Article
- Oxidative Stress-Related Mechanisms in Schizophrenia Pathogenesis and New Treatment Perspectives.Oxidative medicine and cellular longevity · 2021Review
- Overexpression of Toll-Like Receptor 4 Affects Autophagy, Oxidative Stress, and Inflammatory Responses in Monocytes of Transgenic Sheep.Frontiers in cell and developmental biology · 2020Article
- Immunity toMicrobiology spectrum · 2019Review
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- Thrombin-derived host defence peptide modulates neutrophil rolling and migration in vitro and functional response in vivo.Scientific reports · 2017Article
- NADPH oxidases in oxidant production by microglia: activating receptors, pharmacology and association with disease.British journal of pharmacology · 2017Review
- Tempol, a Superoxide Dismutase Mimetic Agent, Inhibits Superoxide Anion-Induced Inflammatory Pain in Mice.BioMed research international · 2017Article
- Toll-Like Receptor 4 Reduces Oxidative Injury via Glutathione Activity in Sheep.Oxidative medicine and cellular longevity · 2016Article
- Toll-Like Receptor 4 Promotes NO Synthesis by Upregulating GCHI Expression under Oxidative Stress Conditions in Sheep Monocytes/Macrophages.Oxidative medicine and cellular longevity · 2015Article
- Article
- Resistin increases monolayer permeability of human coronary artery endothelial cells.PloS one · 2013Article
- MUNC13-4 protein regulates the oxidative response and is essential for phagosomal maturation and bacterial killing in neutrophils.The Journal of biological chemistry · 2012Article
- NOX enzymes: potential target for the treatment of acute lung injury.Cellular and molecular life sciences : CMLS · 2012Review
- Vesicular trafficking through cortical actin during exocytosis is regulated by the Rab27a effector JFC1/Slp1 and the RhoA-GTPase-activating protein Gem-interacting protein.Molecular biology of the cell · 2012Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Exposure of neutrophils to LPS (lipopolysaccharide) triggers their oxidative response. However, the relationship between the signalling downstream of TLR4 (Toll-like receptor 4) after LPS stimulation and the activation of the oxidase remains elusive. Phosphorylation of the cytosolic factor p47phox is essential for activation of the NADPH oxidase. In the present study, we examined the hypothesis that IRAK-4 (interleukin-1 receptor-associated kinase-4), the main regulatory kinase downstream of TLR4 activation, regulates the NADPH oxidase through phosphorylation of p47phox. We show that p47phox is a substrate for IRAK-4. Unlike PKC (protein kinase C), IRAK-4 phosphorylates p47phox not only at serine residues, but also at threonine residues. Target residues were identified by tandem MS, revealing a novel threonine-rich regulatory domain. We also show that p47phox is phosphorylated in granulocytes in response to LPS stimulation. LPS-dependent phosphorylation of p47phox was enhanced by the inhibition of p38 MAPK (mitogen-activated protein kinase), confirming that the kinase operates upstream of p38 MAPK. IRAK-4-phosphorylated p47phox activated the NADPH oxidase in a cell-free system, and IRAK-4 overexpression increased NADPH oxidase activity in response to LPS. We have shown that endogenous IRAK-4 interacts with p47phox and they co-localize at the plasma membrane after LPS stimulation, using immunoprecipitation assays and immunofluorescence microscopy respectively. IRAK-4 was activated in neutrophils in response to LPS stimulation. We found that Thr133, Ser288 and Thr356, targets for IRAK-4 phosphorylation in vitro, are also phosphorylated in endogenous p47phox after LPS stimulation. We conclude that IRAK-4 phosphorylates p47phox and regulates NADPH oxidase activation after LPS stimulation.
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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.