Role of the Rho GTPase Rac in the activation of the phagocyte NADPH oxidase: outsourcing a key task.
Role of the Rho GTPase Rac in the activation of the phagocyte NADPH oxidase: outsourcing a key task.
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DOI：
10.4161/sgtp.27952
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发表时间：
2014-01-01
期刊：
影响因子：
--
通讯作者：
Pick, Edgar
中科院分区：
文献类型：
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作者：
Pick, Edgar
吞噬细胞的产生超氧化物的NADPH氧化酶由膜相关细胞色素B 558（Nox 2和p22（phox）的异二聚体）和4种胞质组分组成：p47（phox）、p67（phox）、p40（phox）和与RhoGDI复合的小GTdR、Rac。超氧化物是由NADPH驱动的分子氧还原，通过位于Nox 2的氧化还原梯度产生的。Nox 2中的电子流通过与胞质组分的相互作用而启动，胞质组分易位到膜，p67（phox）起核心作用。Rac的参与以以下顺序表示：（1）RacGDP-RhoGDI复合物易位至膜;（2）RacGDP从RhoGDI解离;（3）Rac上的GDP至GTP交换，由鸟嘌呤核苷酸交换因子介导;（4）RacGTP与p67（phox）结合;（5）诱导p67（phox）的构象变化，促进与Nox 2的相互作用。Rac在NADPH氧化酶组装中的具体参与通常用作Rho GTP酶的信号传导的范例。
The superoxide-generating NADPH oxidase of phagocytes consists of the membrane-associated cytochrome b 558 (a heterodimer of Nox2 and p22(phox)) and 4 cytosolic components: p47(phox), p67(phox), p40(phox), and the small GTPase, Rac, in complex with RhoGDI. Superoxide is produced by the NADPH-driven reduction of molecular oxygen, via a redox gradient located in Nox2. Electron flow in Nox2 is initiated by interaction with cytosolic components, which translocate to the membrane, p67(phox) playing the central role. The participation of Rac is expressed in the following sequence: (1) Translocation of the RacGDP-RhoGDI complex to the membrane; (2) Dissociation of RacGDP from RhoGDI; (3) GDP to GTP exchange on Rac, mediated by a guanine nucleotide exchange factor; (4) Binding of RacGTP to p67(phox); (5) Induction of a conformational change in p67(phox), promoting interaction with Nox2. The particular involvement of Rac in NADPH oxidase assembly serves as a paradigm for signaling by Rho GTPases, in general.