ArticleThe Journal of biological chemistry2014
Molecular insights of p47phox phosphorylation dynamics in the regulation of NADPH oxidase activation and superoxide production.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 61 citations in OpenAlex.
- NADPH oxidases in immunometabolism and disease pathology: mechanistic networks, pollutant triggers, and therapeutic frontiers.Cellular & molecular immunology · 2026Review
- Antioxidant and Anti-Inflammatory Constituents from the Roots ofAntioxidants (Basel, Switzerland) · 2026Article
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- Computational studies on the functional and structural impact of pathogenic mutations in enzymes.Protein science : a publication of the Protein Society · 2025Review
- NCF-1 plays a pivotal role in the survival of adenocarcinoma cells of pancreatic and gastric origins.In vitro cellular & developmental biology. Animal · 2024Article
- Oligomeric Tau-induced oxidative damage and functional alterations in cerebral endothelial cells: Role of RhoA/ROCK signaling pathway.Free radical biology & medicine · 2024Article
- Direct Interaction of Minocycline to p47phox Contributes to its Attenuation of TNF-α-Mediated Neuronal PC12 Cell Death: Experimental and Simulation Validation.Cell biochemistry and biophysics · 2024Article
- Molecular mechanisms of endothelial dysfunction in coronary microcirculation dysfunction.Journal of thrombosis and thrombolysis · 2023Review
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- Lipoxin A4 attenuates MSU-crystal-induced NLRP3 inflammasome activation through suppressing Nrf2 thereby increasing TXNRD2.Frontiers in immunology · 2022Article
- Mechanisms underlying unidirectional laminar shear stress-mediated Nrf2 activation in endothelial cells: Amplification of low shear stress signaling by primary cilia.Redox biology · 2021Review
- Impaired respiratory burst contributes to infections in PKCδ-deficient patients.The Journal of experimental medicine · 2021Article
- p47Antioxidants (Basel, Switzerland) · 2021Article
- Dehydro-Tocotrienol-β Counteracts Oxidative-Stress-Induced Diabetes Complications inAntioxidants (Basel, Switzerland) · 2021Article
- Research progress on the molecular mechanism of coronary microvascular endothelial cell dysfunction.International journal of cardiology. Heart & vasculature · 2021Review
- Cyclophilin 19 secreted in the host cell cytosol by Trypanosoma cruzi promotes ROS production required for parasite growth.Cellular microbiology · 2021Article
- Advances in Understanding TKS4 and TKS5: Molecular Scaffolds Regulating Cellular Processes from Podosome and Invadopodium Formation to Differentiation and Tissue Homeostasis.International journal of molecular sciences · 2020Review
- Strenuous Acute Exercise Induces Slow and Fast Twitch-Dependent NADPH Oxidase Expression in Rat Skeletal Muscle.Antioxidants (Basel, Switzerland) · 2020Article
- Loss of GTPase activating protein neurofibromin stimulates paracrine cell communication via macropinocytosis.Redox biology · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Phagocyte superoxide production by a multicomponent NADPH oxidase is important in host defense against microbial invasion. However inappropriate NADPH oxidase activation causes inflammation. Endothelial cells express NADPH oxidase and endothelial oxidative stress due to prolonged NADPH oxidase activation predisposes many diseases. Discovering the mechanism of NADPH oxidase activation is essential for developing novel treatment of these diseases. The p47(phox) is a key regulatory subunit of NADPH oxidase; however, due to the lack of full protein structural information, the mechanistic insight of p47(phox) phosphorylation in NADPH oxidase activation remains incomplete. Based on crystal structures of three functional domains, we generated a computational structural model of the full p47(phox) protein. Using a combination of in silico phosphorylation, molecular dynamics simulation and protein/protein docking, we discovered that the C-terminal tail of p47(phox) is critical for stabilizing its autoinhibited structure. Ser-379 phosphorylation disrupts H-bonds that link the C-terminal tail to the autoinhibitory region (AIR) and the tandem Src homology 3 (SH3) domains, allowing the AIR to undergo phosphorylation to expose the SH3 pocket for p22(phox) binding. These findings were confirmed by site-directed mutagenesis and gene transfection of p47(phox-/-) coronary microvascular cells. Compared with wild-type p47(phox) cDNA transfected cells, the single mutation of S379A completely blocked p47(phox) membrane translocation, binding to p22(phox) and endothelial O2(·-) production in response to acute stimulation of PKC. p47(phox) C-terminal tail plays a key role in stabilizing intramolecular interactions at rest. Ser-379 phosphorylation is a molecular switch which initiates p47(phox) conformational changes and NADPH oxidase-dependent superoxide production by cells.
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