PMID- 1660188 OWN - NLM STAT- MEDLINE DCOM- 19920109 LR - 20220225 IS - 0036-8075 (Print) IS - 0036-8075 (Linking) VI - 254 IP - 5037 DP - 1991 Dec 6 TI - Regulation of phagocyte oxygen radical production by the GTP-binding protein Rac 2. PG - 1512-5 AB - 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. FAU - Knaus, U G AU - Knaus UG AD - Department of Immunology, Scripps Research Institute, La Jolla, CA 92037. FAU - Heyworth, P G AU - Heyworth PG FAU - Evans, T AU - Evans T FAU - Curnutte, J T AU - Curnutte JT FAU - Bokoch, G M AU - Bokoch GM LA - eng GR - AI24838/AI/NIAID NIH HHS/United States GR - GM39434/GM/NIGMS NIH HHS/United States GR - HL48008/HL/NHLBI NIH HHS/United States GR - etc. PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Science JT - Science (New York, N.Y.) JID - 0404511 RN - 0 (Free Radicals) RN - 11062-77-4 (Superoxides) RN - EC 1.6.- (NADH, NADPH Oxidoreductases) RN - EC 1.6.3.- (NADPH Oxidases) RN - EC 3.6.1.- (GTP-Binding Proteins) RN - EC 3.6.5.2 (rac GTP-Binding Proteins) SB - IM GS - Rac1 GS - Rac2 MH - Amino Acid Sequence MH - Free Radicals MH - GTP-Binding Proteins/*physiology MH - Humans MH - In Vitro Techniques MH - Molecular Sequence Data MH - NADH, NADPH Oxidoreductases/*metabolism MH - NADPH Oxidases MH - Neutrophils/*physiology MH - *Respiratory Burst MH - Superoxides/metabolism MH - rac GTP-Binding Proteins EDAT- 1991/12/06 00:00 MHDA- 1991/12/06 00:01 CRDT- 1991/12/06 00:00 PHST- 1991/12/06 00:00 [pubmed] PHST- 1991/12/06 00:01 [medline] PHST- 1991/12/06 00:00 [entrez] AID - 10.1126/science.1660188 [doi] PST - ppublish SO - Science. 1991 Dec 6;254(5037):1512-5. doi: 10.1126/science.1660188.