ArticleThe Journal of biological chemistry2008
Identification of a conserved Rac-binding site on NADPH oxidases supports a direct GTPase regulatory mechanism.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 74 citations in OpenAlex.
- NADPH Oxidase 3: Beyond the Inner Ear.Antioxidants (Basel, Switzerland) · 2024Review
- Multiple Immune Defects in Two Patients with Novel DOCK2 Mutations Result in Recurrent Multiple Infection Including Live Attenuated Virus Vaccine.Journal of clinical immunology · 2023Article
- SLAMF8 Downregulates Mouse Macrophage Microbicidal MechanismsFrontiers in immunology · 2022Article
- Regulation of NADPH Oxidase-Mediated Superoxide Production by Acetylation and Deacetylation.Frontiers in physiology · 2021Article
- Evolutionary and functional analysis of the plant-specific NADPH oxidase gene family inRoyal Society open science · 2019Article
- RCC2 over-expression in tumor cells alters apoptosis and drug sensitivity by regulating Rac1 activation.BMC cancer · 2018Article
- NADPH oxidase in brain injury and neurodegenerative disorders.Molecular neurodegeneration · 2017Review
- NOX Modifiers-Just a Step Away from Application in the Therapy of Airway Inflammation?Antioxidants & redox signaling · 2015Review
- Evolution of NADPH Oxidase Inhibitors: Selectivity and Mechanisms for Target Engagement.Antioxidants & redox signaling · 2015Review
- Nox family NADPH oxidases in mechano-transduction: mechanisms and consequences.Antioxidants & redox signaling · 2014Review
- Role of the Rho GTPase Rac in the activation of the phagocyte NADPH oxidase: outsourcing a key task.Small GTPases · 2014Review
- Strategies for identifying synthetic peptides to act as inhibitors of NADPH oxidases, or "all that you did and did not want to know about Nox inhibitory peptides".Cellular and molecular life sciences : CMLS · 2012Review
- Towards specific NADPH oxidase inhibition by small synthetic peptides.Cellular and molecular life sciences : CMLS · 2012Review
- Biochemistry, physiology, and pathophysiology of NADPH oxidases in the cardiovascular system.Circulation research · 2012Review
- Rational design of small molecule inhibitors targeting the Rac GTPase-p67(phox) signaling axis in inflammation.Chemistry & biology · 2012Article
- c-Src-mediated phosphorylation of NoxA1 and Tks4 induces the reactive oxygen species (ROS)-dependent formation of functional invadopodia in human colon cancer cells.Molecular biology of the cell · 2010Article
- A novel and specific NADPH oxidase-1 (Nox1) small-molecule inhibitor blocks the formation of functional invadopodia in human colon cancer cells.ACS chemical biology · 2010Article
- A conserved region between the TPR and activation domains of p67phox participates in activation of the phagocyte NADPH oxidase.The Journal of biological chemistry · 2010Article
- A prenylated p47phox-p67phox-Rac1 chimera is a Quintessential NADPH oxidase activator: membrane association and functional capacity.The Journal of biological chemistry · 2010Article
- Nicotinamide adenine dinucleotide phosphate reduced oxidase 5 (Nox5) regulation by angiotensin II and endothelin-1 is mediated via calcium/calmodulin-dependent, rac-1-independent pathways in human endothelial cells.Circulation research · 2010Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The NADPH oxidases (Noxs) are a family of superoxide-generating enzymes implicated in a variety of biological processes. Full activity of Nox1, -2, and -3 requires the action of a Rac GTPase. A direct regulatory interaction of Rac with Nox2 has been proposed as part of a two-step mechanism for regulating electron transfer during superoxide formation. Using truncation analysis of Rac binding to the cytoplasmic tail of Nox2, along with peptides derived from this region in cell-free assays, we identify a Rac interaction site within amino acids 419-430 of Nox2. This region is required for binding Rac2 but not p47(phox) or p67(phox) cytosolic regulatory factors. A cell-permeant version of the peptide encompassing amino acids 419-430 specifically inhibits NADPH oxidase activation in intact human neutrophils. Mutational analysis of the putative Rac-binding site revealed specific residues, particularly Lys-421, Tyr-425, and Lys-426, individually required for Rac-dependent NADPH oxidase activity that are conserved in the Rac-regulated Nox1, Nox2, and Nox3 enzymes but not in Nox4 or Nox5. Mutation of the conserved residues in the Rac-binding site of Nox1 also result in the loss of Rac-dependent activity. Our data identify a functional Rac interaction site conserved in Rac-dependent Noxs and support a direct regulatory interaction of Rac GTPases to promote activation of these NADPH oxidases.
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