ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2009
Regulation of the phagocyte NADPH oxidase activity: phosphorylation of gp91phox/NOX2 by protein kinase C enhances its diaphorase activity and binding to Rac2, p67phox, and p47phox.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 184 citations in OpenAlex.
- Analysis of the sorghumGM crops & food · 2026Article
- IL-17A Promotes NETs Formation via the PKCζ-ERK-ROS-PAD4 Pathway in a Mouse Model of Ischemic Stroke.CNS neuroscience & therapeutics · 2026Article
- Exploring the involvement of serine proteases in neutrophil extracellular traps: a review of mechanisms and implications.Cell death & disease · 2025Review
- Targeting NADPH Oxidase as an Approach for Diabetic Bladder Dysfunction.Antioxidants (Basel, Switzerland) · 2024Review
- Mitochondrial Plasticity and Glucose Metabolic Alterations in Human Cancer under Oxidative Stress-From Viewpoints of Chronic Inflammation and Neutrophil Extracellular Traps (NETs).International journal of molecular sciences · 2024Review
- NCF4 regulates antigen presentation of cysteine peptides by intracellular oxidative response and restricts activation of autoreactive and arthritogenic T cells.Redox biology · 2024Article
- Decreased LPS-induced lung injury in pigs treated with a lung surfactant protein A-derived nonapeptide that inhibits peroxiredoxin 6 activity and subsequent NOX1,2 activation.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- ROCK2 interacts with p22phox to phosphorylate p47phox and to control NADPH oxidase activation in human monocytes.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Review
- Review
- Regulation of Neutrophil NADPH Oxidase, NOX2: A Crucial Effector in Neutrophil Phenotype and Function.Frontiers in cell and developmental biology · 2022Review
- Self-Sustained Regulation or Self-Perpetuating Dysregulation: ROS-dependent HIF-YAP-Notch Signaling as a Double-Edged Sword on Stem Cell Physiology and Tumorigenesis.Frontiers in cell and developmental biology · 2022Review
- Prolyl-Isomerase Pin1 Controls Key fMLP-Induced Neutrophil Functions.Biomedicines · 2021Article
- Attenuating vascular stenosis-induced astrogliosis preserves white matter integrity and cognitive function.Journal of neuroinflammation · 2021Article
- Oxidative stress induced by NOX2 contributes to neuropathic pain via plasma membrane translocation of PKCε in rat dorsal root ganglion neurons.Journal of neuroinflammation · 2021Article
- Adipocyte, Immune Cells, and miRNA Crosstalk: A Novel Regulator of Metabolic Dysfunction and Obesity.Cells · 2021Review
- Pro-Resolving FPR2 Agonists Regulate NADPH Oxidase-Dependent Phosphorylation of HSP27, OSR1, and MARCKS and Activation of the Respective Upstream Kinases.Antioxidants (Basel, Switzerland) · 2021Article
- Inhibitors of Src Family Kinases, Inducible Nitric Oxide Synthase, and NADPH Oxidase as Potential CNS Drug Targets for Neurological Diseases.CNS drugs · 2021Review
- Membranous NOX5-derived ROS oxidizes and activates local Src to promote malignancy of tumor cells.Signal transduction and targeted therapy · 2020Article
- The Interplay between Oxidative Stress and miRNAs in Obesity-Associated Hepatic and Vascular Complications.Antioxidants (Basel, Switzerland) · 2020Review
28 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
Abstract
Neutrophils generate microbicidal oxidants through activation of a multicomponent enzyme called NADPH oxidase. During activation, the cytosolic NADPH oxidase components (p47(phox), p67(phox), p40(phox), and Rac2) translocate to the membranes, where they associate with flavocytochrome b(558), which is composed of gp91(phox)/NOX2 and p22(phox), to form the active system. During neutrophil stimulation, p47(phox), p67(phox), p40(phox), and p22(phox) are phosphorylated; however, the phosphorylation of gp91(phox)/NOX2 and its potential role have not been defined. In this study, we show that gp91(phox) is phosphorylated in stimulated neutrophils. The gp91(phox) phosphoprotein is absent in neutrophils from chronic granulomatous disease patients deficient in gp91(phox), which confirms that this phosphoprotein is gp91(phox). The protein kinase C inhibitor GF109203X inhibited phorbol 12-myristate 13-acetate-induced phosphorylation of gp91(phox), and protein kinase C (PKC) phosphorylated the recombinant gp91(phox)- cytosolic carboxy-terminal flavoprotein domain. Two-dimensional tryptic peptide mapping analysis showed that PKC phosphorylated the gp91(phox)-cytosolic tail on the same peptides that were phosphorylated on gp91(phox) in intact cells. In addition, PKC phosphorylation increased diaphorase activity of the gp91(phox) flavoprotein cytosolic domain and its binding to Rac2, p67(phox), and p47(phox). These results demonstrate that gp91(phox) is phosphorylated in human neutrophils by PKC to enhance its catalytic activity and assembly of the complex. Phosphorylation of gp91(phox)/NOX2 is a novel mechanism of NADPH oxidase regulation.
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