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Science 6 December 1991:
Vol. 254. no. 5037, pp. 1512 - 1515
DOI: 10.1126/science.1660188

Articles

Science, Vol 254, Issue 5037, 1512-1515
Copyright © 1991 by American Association for the Advancement of Science


articles

Regulation of phagocyte oxygen radical production by the GTP-binding protein Rac 2

UG Knaus, PG Heyworth, T Evans, JT Curnutte, and GM Bokoch

Department of Immunology, Scripps Research Institute, La Jolla, CA 92037.

A major action of the microbicidal system of human neutrophils is the formation of superoxide anion (O2-) 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 (Gox) that regulates the NADPH oxidase of neutrophils was identified. Gox was purified and shown to augment the rate of O2- production in a cell-free oxidase activation system. Sequence analysis of peptide fragments from Gox 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 O2- 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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R. W. Erickson, P. Langel-Peveri, A. E. Traynor-Kaplan, P. G. Heyworth, and J. T. Curnutte (1999)
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Essential Requirement of Cytosolic Phospholipase A2 for Activation of the H+ Channel in Phagocyte-like Cells.
A. Lowenthal and R. Levy (1999)
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   Abstract »    Full Text »    PDF »
Isolation and Characterization of a Variant HL60 Cell Line Defective in the Activation of the NADPH Oxidase by Phorbol Myristate Acetate.
M. Tardif, M.-J. Rabiet, T. Christophe, M.-D. Milcent, and F. Boulay (1998)
J. Immunol. 161, 6885-6895
   Abstract »    Full Text »    PDF »
Role of Histidines Identified by Mutagenesis in the NADPH Oxidase-associated H+ Channel.
L. M. Henderson (1998)
J. Biol. Chem. 273, 33216-33223
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Prostaglandin F2{alpha} Treatment In Vivo, but Not In Vitro, Stimulates Protein Kinase C-Activated Superoxide Production by Nonsteroidogenic Cells of the Rat Corpus Luteum.
R. F. Aten, T. R. Kolodecik, M. J. Rossi, C. Debusscher, and H. R. Behrman (1998)
Biol Reprod 59, 1069-1076
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Effect of Cytotoxic Necrotizing Factor-1 on Actin Cytoskeleton in Human Monocytes: Role in the Regulation of Integrin-Dependent Phagocytosis.
C. Capo, S. Meconi, M.-V. Sanguedolce, N. Bardin, G. Flatau, P. Boquet, and J.-L. Mege (1998)
J. Immunol. 161, 4301-4308
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Structural Requirements for PAK Activation by Rac GTPases.
U. G. Knaus, Y. Wang, A. M. Reilly, D. Warnock, and J. H. Jackson (1998)
J. Biol. Chem. 273, 21512-21518
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Essential Requirement of Cytosolic Phospholipase A2 for Activation of the Phagocyte NADPH Oxidase.
R. Dana, T. L. Leto, H. L. Malech, and R. Levy (1998)
J. Biol. Chem. </