Knaus U G, Heyworth P G, Evans T, Curnutte J T, Bokoch G M
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037.
Science. 1991 Dec 6;254(5037):1512-5. doi: 10.1126/science.1660188.
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.
人类中性粒细胞杀菌系统的一个主要作用是通过一种多组分氧化酶形成超氧阴离子（O2-），该氧化酶将电子从还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH）转移到分子氧。氧化酶从其胞质和膜结合成分组装和激活的机制尚不清楚，但可能需要鸟苷5'-三磷酸（GTP）结合成分的活性。一种调节中性粒细胞NADPH氧化酶的胞质GTP结合蛋白（Gox）被鉴定出来。Gox被纯化，并显示在无细胞氧化酶激活系统中可提高O2-的产生速率。对Gox肽片段的序列分析确定它为Rac 2，是GTP结合蛋白Ras超家族的成员。针对Rac 2羧基末端衍生肽的抗体以浓度依赖的方式抑制O2-的产生。这些结果表明Rac 2是人类中性粒细胞NADPH氧化酶的调节成分，并为该氧自由基产生系统的调节机制提供了新的见解。
