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p40 phox , a third cytosolic component of the activation complex of the NADPH oxidase to contain src homology 3 domains
Open accessAbstract
The NADPH oxidase generates superoxide in phagocytic cells. It is important for immunity and its deficiency leads to chronic granulomatous disease (CGD). It consists of a membrane-bound flavocytochrome b that lies dormant until activated by the translocation to the plasma membrane of cytosolic proteins, p47phox (phox for phagocyte oxidase), p67phox and p21rac, a small GTP-binding protein. We show here that a novel component, p40phox, forms an activation complex with p47phox and p67phox with which it translocates to the membrane to associate with the flavocytochrome b. cDNA cloning and amino acid analysis revealed that p40phox has an src homology 3 (SH3) domain and a large region of sequence similarity with the N-terminus of p47phox. The primary association of p40phox appears to be with p67phox, and it is present in reduced amounts in patients with CGD lacking p67phox.
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“For example, H2O2 can also modulate genes expression by epigenetic modification and activate transcription factors such as AP-1, NRF2, CREB, HSF1, HIF-1, TP53, NF-κβ, NOTCH, SP1, SCREB-1 and FOXO family [14,15,16,17,18,19,20,21,22].”
From The Role of Reactive Species on Innate Immunity (2022) · cites this paper as [20]
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Metadata
- Authors
- Wientjes, F. B., Hsuan, J. J., Totty, N. F., & Segal, A. W.
- Affiliations
- University College London (GB)
- Ludwig Cancer Research (GB)
- ORCID
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 1993-12-15
- Volume
- 296
- Issue
- 3
- Pages
- 557-561
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1137734
- OpenAlex
- W1727958888
- Cited by
- 301
- References
- 27
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 3 · 2023: 9 · 2022: 4 · 2021: 7 · 2020: 3 · 2019: 6 · 2018: 3 · 2017: 6 · 2016: 6 · 2015: 6 · 2014: 11 · 2013: 11 · 2012: 2
- FWCI
- 6.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Keywords
- p40phox, NADPH oxidase, superoxide production, chronic granulomatous disease, p47phox, p67phox, Src homology 3 domain, membrane translocation, phagocytes, G proteins
- MeSH terms
- Amino Acid Sequence, Base Sequence, Biological Transport, Cell Membrane, Cloning, Molecular, Enzyme Activation, Granulomatous Disease, Chronic, Humans, Molecular Sequence Data, NADH, NADPH Oxidoreductases, Neutrophils, Phosphoproteins, Genes, src, Sequence Homology, Amino Acid, DNA, Complementary, NADPH Oxidases
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