REGULATION OF PHAGOCYTE OXYGEN RADICAL PRODUCTION BY THE GTP-BINDING PROTEIN RAC-2
REGULATION OF PHAGOCYTE OXYGEN RADICAL PRODUCTION BY THE GTP-BINDING PROTEIN RAC-2
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DOI：
10.1126/science.1660188
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发表时间：
1991-12-06
期刊：
影响因子：
56.9
通讯作者：
BOKOCH, GM
中科院分区：
文献类型：
--
作者：
KNAUS, UG;HEYWORTH, PG;BOKOCH, GM
人嗜中性粒细胞的杀微生物系统的主要作用是通过多组分氧化酶形成超氧阴离子（O2-），该多组分氧化酶将电子从还原形式的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组分组装和活化的机制尚不清楚，但可能需要鸟苷5 '-三磷酸（GTP）结合组分的活性。鉴定了调节中性粒细胞NADPH氧化酶的胞质GTP结合蛋白（G（ox））。G（ox）被纯化，并显示在无细胞氧化酶活化系统中增加O2-产生的速率。来自G（ox）的肽片段的序列分析将其鉴定为Rac 2，其为GTP结合蛋白的Ras超家族的成员。抗Rac 2羧基端肽抗体以浓度依赖性方式抑制O2生成。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，并提供了新的见解，该氧自由基生成系统的调节机制。
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 (G(ox)) that regulates the NADPH oxidase of neutrophils was identified. G(ox) was purified and shown to augment the rate of O2- 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 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.