P562C, A NOVEL C2 DOMAIN PROTEIN OF LEUKOCYTES

P562C，一种新型白细胞 C2 结构域蛋白

• 批准号: 2650067
• 负责人: Bernard M Babior
• 金额: $ 19.47万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2650067
• 关键词: B lymphocyte; NAD(P)H dehydrogenase; cell free system; chimeric proteins; enzyme activity; genetically modified animals; green fluorescent proteins; guanine nucleotide binding protein; human tissue; immunoprecipitation; laboratory mouse; laboratory rabbit; neutrophil; phosphorylation; polymerase chain reaction; protein structure function; yeast two hybrid system

The leukocyte NADPH oxidase catalyzes the production of O2 from oxygen and NADPH. The yeast 2-hybrid system was used to look for proteins the interact with p67, one of the cytosolic subunits of the oxidase. This system identified a B lymphocyte cDNA that encoded a 56 kDa protein containing two Ca++ and lipid-binding C2 domains in its C-terminal half. Rabphilin-3A, a Rab3a-binding protein involved in synaptic vesicle trafficking, has a similar C2 domain structure, suggesting that the new protein, designated p56C2 and characterize it in terms of its location in neutrophils and B lymphocytes, its interactions with other leukocyte proteins and with the cortical cytoskeleton, and its association with lipids. The function of p56C2 will be studied by examining its effect on oxidase activation in the phosphorylation-dependent oxidase activating system, by examining oxidase activation and secretory vesicle fusion in cells depleted of the protein by antisense techniques, and by studying a transgenic mouse deficient in the protein. Particular attention will be paid to the possibility that p56C2 interacts with Rap1A, a small guanine nucleotide-binding protein that copurifies with the membrane- associated subunits of the oxidase. Through these experiments we hope to achieve a deeper understanding of the activation of the O2- forming oxidase of leukocytes, and enzyme important in host defense and in the harmful side effects of inflammation.

白细胞NADPH氧化酶催化O2的产生