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Activation of the phagocyte NADPH oxidase and its disorders

Activation of the phagocyte NADPH oxidase and its disorders
吞噬细胞 NADPH 氧化酶的激活及其紊乱
批准号:
09470045
负责人:
TAKESHIGE Koichiro
金额:
$5.12万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B).
财政年份:
1997
资助国家:
日本
项目状态:
已结题
起止时间:
1997 至 2000

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中文摘要
翻译
处于休眠状态的中性粒细胞NADPH氧化酶被激活,产生超氧化物,这是其他活性氧的前体,参与杀死吞噬的细菌和参与炎症。NADPH氧化酶由膜整合的黄细胞素b_(558)和p22(?)当含有SH3结构域的两个胞质因子p47;lt;Phox>和p67;lt;Phox>,小的GTP结合蛋白Rac和另一个胞质因子p40;此外,在氧化酶激活过程中,胞质因子被磷酸化。组装过程是受调控的,涉及到氧化酶因子之间的多个结合作用,从而产生活性的氧化酶复合体。本研究证明了p47^<Phox>与细胞色素b_<558>,p67^<Phox>与Rac,以及p40^<Phox>和p67^<Phox>与细胞色素b_<558>和Rac,以及p40^<Phox>和p67^<Phox>之间发生了特异性的分子相互作用,导致了氧化酶的激活。
英文摘要
The neutrophil NADPH oxidase, dormant in resting state, is activated to produce superoxide, which is a precursor of other active oxygens which involved in killing of phagocytozed bacteria and in inflammation. The NADPH oxidase consists of a membrane-integrated flavocytochrome b_<558> comprising two subunits, gp91^<phox> and p22^<phox>. Activation of the oxidase occurs when two cytosolic SH3 domain-containing factors, p47^<phox> and p67^<phox>, the small GTP-binding protein Rac and another cytosolic factor, p40^<phox>, assemble and translocate to the plasma membrane. In addition, the cytosolic factors are phosphorylated during oxidase activation. The assembly process is regulated and involves multiple binding interactions between the oxidase factors, resulting in an active oxidase complex. It has been demonstrated in this study that the specific molecular interactions occuring between p47^<phox> and cytochrome b_<558>, p67^<phox> and Rac, and p40^<phox> and p67^<phox>, leading to activation of the oxidase.
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会议论文
Koga H.: "Tetratricopeptide repeat (TPR) motifs of p67phox patricipate in interaction with th small GTPase Rac and activation of the phagocyte NADPH oxidase."J. Biol. Chem.. 274. 25051-25060 (1999)
Koga H.:“p67phox patricipate 的四肽重复 (TPR) 基序与小 GTPase Rac 相互作用并激活吞噬细胞 NADPH 氧化酶。”J.
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通讯作者:
Mizuki K.: "Functional modules and expression of mouse p40^<Phox> and p67^<Phox>,SH3-domain-containing proteins involved in the phagocyte NADPH oxidase complex" Eur.J.Biochem.(in press).
Mizuki K.:“小鼠 p40^<Phox> 和 p67^<Phox> 的功能模块和表达,参与吞噬细胞 NADPH 氧化酶复合物的包含 SH3 结构域的蛋白质”Eur.J.Biochem.(出版中)。
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Irie,T. et al.: "TAK1 mediates an activation signal from toll-like receptor (s) to unclear factor-κB in lipopolysaccharide-stimulated macrophages."FEBS Lett.. 467. 160-164 (2000)
Irie, T. 等人:“TAK1 在脂多糖刺激的巨噬细胞中介导从 Toll 样受体到不清楚的因子 κB 的激活信号。” FEBS Lett.. 467. 160-164 (2000)
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共 36 条
    Studies on stimulus-specific induction of a novel NF-κB regulator, IκB-ζ, and its physiological roles
    • 批准号:
      17590252
    • 项目类别:
      Grant-in-Aid for Scientific Research (C)
    • 资助金额:
      $2.24万
    • 财政年份:
      2005
    • 负责人:
      TAKESHIGE Koichiro
    • 依托单位:
    Studies on the phagocyte-specific NADPH oxidase involving in the killing of micro organisms and cell damage and the mechanism of activation
    • 批准号:
      04454173
    • 项目类别:
      Grant-in-Aid for General Scientific Research (B)
    • 资助金额:
      $4.1万
    • 财政年份:
      1992
    • 负责人:
      TAKESHIGE Koichiro
    • 依托单位:
    海外基金