ArticleThe Journal of biological chemistry2010
p47phox Phox homology domain regulates plasma membrane but not phagosome neutrophil NADPH oxidase activation.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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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.
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Who cites it
25 citing papers in PubMed, 48 citations in OpenAlex.
- Human inborn errors of the phagocyte respiratory burst: Chronic granulomatous disease and beyond.Journal of human immunity · 2026Article
- Regulatory effects of beta-2-microglobulin on reactive oxygen species generation in polymorphonuclear cells.Scientific reports · 2026Article
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- The systemic lupus erythematosus-associated NCF1Nature communications · 2025Article
- NETs: a new target for autoimmune disease.Frontiers in immunology · 2025Review
- Article
- Human blood neutrophils generate ROS through FcγR-signaling to mediate protection against febrile P. falciparum malaria.Communications biology · 2023Article
- Meta-Analysis and Systematic Review of the Association between a HypoactiveAntioxidants (Basel, Switzerland) · 2022Review
- The NCF1 variant p.R90H aggravates autoimmunity by facilitating the activation of plasmacytoid dendritic cells.The Journal of clinical investigation · 2022Article
- Regulation of Neutrophil NADPH Oxidase, NOX2: A Crucial Effector in Neutrophil Phenotype and Function.Frontiers in cell and developmental biology · 2022Review
- Nicotinamide Adenine Dinucleotide Phosphate Oxidases Are Everywhere in Brain Disease, but Not in Huntington's Disease?Frontiers in aging neuroscience · 2021Review
- Mechanistic computational modeling of the kinetics and regulation of NADPH oxidase 2 assembly and activation facilitating superoxide production.Free radical research · 2020Article
- Review
- Haploinsufficiency of NADPH Oxidase Subunit Neutrophil Cytosolic Factor 2 Is Sufficient to Accelerate Full-Blown Lupus in NZM 2328 Mice.Arthritis & rheumatology (Hoboken, N.J.) · 2017Article
- A missense variant in NCF1 is associated with susceptibility to multiple autoimmune diseases.Nature genetics · 2017Article
- Neutrophils to the ROScue: Mechanisms of NADPH Oxidase Activation and Bacterial Resistance.Frontiers in cellular and infection microbiology · 2017Review
- Role of p85α in neutrophil extra- and intracellular reactive oxygen species generation.Oncotarget · 2016Article
- Protein-tyrosine phosphatase Shp2 positively regulates macrophage oxidative burst.The Journal of biological chemistry · 2015Article
- Article
- New insights into the regulation of neutrophil NADPH oxidase activity in the phagosome: a focus on the role of lipid and Ca(2+) signaling.Antioxidants & redox signaling · 2013Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The assembly of cytosolic subunits p47(phox), p67(phox), and p40(phox) with flavocytochrome b(558) at the membrane is required for activating the neutrophil NADPH oxidase that generates superoxide for microbial killing. The p47(phox) subunit plays a critical role in oxidase assembly. Recent studies showed that the p47(phox) Phox homology (PX) domain mediates phosphoinositide binding in vitro and regulates phorbol ester-induced NADPH oxidase activity in a K562 myeloid cell model. Because the importance of the p47(phox) PX domain in neutrophils is unclear, we investigated its role using p47(phox) knock-out (KO) mouse neutrophils to express human p47(phox) and derivatives harboring R90A mutations in the PX domain that result in loss of phosphoinositide binding. Human p47(phox) proteins were expressed at levels similar to endogenous murine p47(phox), with the exception of a chronic granulomatous disease-associated R42Q mutant that was poorly expressed, and wild type human p47(phox) rescued p47(phox) KO mouse neutrophil NADPH oxidase activity. Plasma membrane NAPDH oxidase activity was reduced in neutrophils expressing p47(phox) with Arg(90) substitutions, with substantial effects on responses to either phorbol ester or formyl-Met-Leu-Phe and more modest effects to particulate stimuli. In contrast, p47(phox) Arg(90) mutants supported normal levels of intracellular NADPH oxidase activity during phagocytosis of a variety of particles and were recruited to phagosome membranes. This study defines a differential and agonist-dependent role of the p47(phox) PX domain for neutrophil NADPH oxidase activation.
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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.