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Regulation of Phagocyte Oxygen Radical Production by the GTP-Binding Protein Rac 2
Abstract
A major action of the microbicidal system of human neutrophils is the formation of superoxide anion (O 2 - ) by a multicomponent oxidase that transfers electrons from the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) to molecular oxygen. The mechanism of assembly and activation of the oxidase from its cytosolic and membrane-bound components is unknown, but may require the activity of a guanosine 5′-triphosphate (GTP)-binding component. A cytosolic GTP-binding protein (G ox ) that regulates the NADPH oxidase of neutrophils was identified. G ox was purified and shown to augment the rate of O 2 - production in a cell-free oxidase activation system. Sequence analysis of peptide fragments from G ox identified it as Rac 2, a member of the Ras superfamily of GTP-binding proteins. Antibody to a peptide derived from the COOH-terminus of Rac 2 inhibited O 2 - generation in a concentration-dependent manner. These results suggest that Rac 2 is a regulatory component of the human neutrophil NADPH oxidase, and provide new insights into the mechanism by which this oxygen radical-generating system is regulated.
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In the citing paper
“Rac2 was demonstrated as an oxidase-related factor in human neutrophils (20).”
From Biochemical and Biological Characterization of a Human Rac2 GTPase Mutant Associated with Phagocytic Immunodeficiency (2001) · cites this paper as [20]
In the citing paper
“RAC2), through interactions with reduced NAD phosphate oxidase component p67 phox , activates neutrophil superoxide production”
From Dominant activating RAC2 mutation with lymphopenia, immunodeficiency, and cytoskeletal defects (2019) · cites this paper as [1]
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Metadata
- Authors
- Knaus, U. G., Heyworth, P. G., Evans, T., Curnutte, J. T., & Bokoch, G. M.
- Venue
- Science
- Published
- 1991-12-06
- Volume
- 254
- Issue
- 5037
- Pages
- 1512-1515
- ISSN
- 0036-8075
- 1095-9203
- Cited by
- 525
- References
- 0
- Language
- en
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- Knaus, U. G., Heyworth, P. G., Evans, T., Curnutte, J. T., & Bokoch, G. M. (1991). Regulation of Phagocyte Oxygen Radical Production by the GTP-Binding Protein Rac 2. Science. https://doi.org/10.1126/science.1660188
