ArticleThe Biochemical journal2006
Activation of the superoxide-producing phagocyte NADPH oxidase requires co-operation between the tandem SH3 domains of p47phox in recognition of a polyproline type II helix and an adjacent alpha-helix of p22phox.
Article in The Biochemical journal, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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.
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.
Who cites it
18 citing papers in PubMed, 42 citations in OpenAlex.
- Molecular Views into the Synthesis and Activation of FlavocytochromeAntioxidants (Basel, Switzerland) · 2026Review
- Case Report: First report of a novel homozygous nonsense mutation in theFrontiers in immunology · 2026Article
- Definition and Discovery of Tandem SH3-Binding Motifs Interacting with Members of the p47Biomolecules · 2025Article
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- NADPH Oxidase 3: Beyond the Inner Ear.Antioxidants (Basel, Switzerland) · 2024Review
- NADPH Oxidases (NOX): An Overview from Discovery, Molecular Mechanisms to Physiology and Pathology.Antioxidants (Basel, Switzerland) · 2021Review
- The Emerging Roles of Nicotinamide Adenine Dinucleotide Phosphate Oxidase 2 in Skeletal Muscle Redox Signaling and Metabolism.Antioxidants & redox signaling · 2019Review
- Identification of a region in p47phox/NCF1 crucial for phagocytic NADPH oxidase (NOX2) activation.Journal of leukocyte biology · 2013Article
- Effects of angiotensin II on the cerebral circulation: role of oxidative stress.Frontiers in physiology · 2012Article
- NADPH oxidase (NOX) isoforms are inhibited by celastrol with a dual mode of action.British journal of pharmacology · 2011Article
- Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets.Nature reviews. Drug discovery · 2011Review
- Characterization of superoxide overproduction by the D-Loop(Nox4)-Nox2 cytochrome b(558) in phagocytes-Differential sensitivity to calcium and phosphorylation events.Biochimica et biophysica acta · 2011Article
- p47phox molecular activation for assembly of the neutrophil NADPH oxidase complex.The Journal of biological chemistry · 2010Article
- Phosphorylation of p22phox on threonine 147 enhances NADPH oxidase activity by promoting p47phox binding.The Journal of biological chemistry · 2010Article
- Article
- Regulation of superoxide production in neutrophils: role of calcium influx.Journal of leukocyte biology · 2008Review
- Molecular evolution of Phox-related regulatory subunits for NADPH oxidase enzymes.BMC evolutionary biology · 2007Article
- Phagocytosis-coupled activation of the superoxide-producing phagocyte oxidase, a member of the NADPH oxidase (nox) family.International journal of hematology · 2006Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of the superoxide-producing phagocyte NADPH oxidase, crucial for host defence, requires an SH3 (Src homology 3)-domain-mediated interaction of the regulatory protein p47phox with p22phox, a subunit of the oxidase catalytic core flavocytochrome b558. Although previous analysis of a crystal structure has demonstrated that the tandem SH3 domains of p47phox sandwich a short PRR (proline-rich region) of p22phox (amino acids 151-160), containing a polyproline II helix, it has remained unknown whether this model is indeed functional in activation of the oxidase. In the present paper we show that the co-operativity between the two SH3 domains of p47phox, as expected from the model, is required for oxidase activation. Deletion of the linker between the p47phox SH3 domains results not only in a defective binding to p22phox but also in a loss of the activity to support superoxide production. The present analysis using alanine-scanning mutagenesis identifies Pro152, Pro156 and Arg158 in the p22phox PRR as residues indispensable for the interaction with p47phox. Pro152 and Pro156 are recognized by the N-terminal SH3 domain, whereas Arg158 contacts with the C-terminal SH3 domain. Amino acid substitution for any of the three residues in the p22phox PRR abrogates the superoxide-producing activity of the oxidase reconstituted in intact cells. The bis-SH3-mediated interaction of p47phox with p22phox thus functions to activate the phagocyte oxidase. Furthermore, we provide evidence that a region C-terminal to the PRR of p22phox (amino acids 161-164), adopting an a-helical conformation, participates in full activation of the phagocyte oxidase by fortifying the association with the p47phox SH3 domains.
Indexed as
Identifiers
What OpenQuestion holds
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.