INTERACTION OF RAC WITH P67(PHOX) AND REGULATION OF PHAGOCYTIC NADPH OXIDASE ACTIVITY
INTERACTION OF RAC WITH P67(PHOX) AND REGULATION OF PHAGOCYTIC NADPH OXIDASE ACTIVITY
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DOI：
10.1126/science.8036496
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发表时间：
1994-07-22
期刊：
影响因子：
56.9
通讯作者：
HALL, A
中科院分区：
文献类型：
--
作者：
DIEKMANN, D;ABO, A;HALL, A
Rho和Rac是鸟苷三磷酸（GIP）结合蛋白Ras超家族的两个成员，在真核细胞中调节多种信号转导途径。通过对吞噬细胞的刺激，Rac增强了烟酰胺腺嘌呤二核苷酸磷酸（还原）（NADPH）氧化酶的活性，导致超氧自由基的产生。NADPH氧化酶的激活需要在质膜上组装一个多分子复合物，该复合物由两个完整的膜蛋白gp91（phox）和p2l（phox）以及两个细胞质蛋白p67（phox）和p47（phox）组成。Rac1以依赖gtp的方式直接与p67（phox）相互作用。在效应位点发生突变的Rac修饰形式不会刺激氧化酶活性或与p67（phox）结合。因此，p67（phox）似乎是NADPH氧化酶复合体中的Rac效应蛋白。
Rho and Rac, two members of the Ras superfamily of guanosine triphosphate (GIP)-binding proteins, regulate a variety of signal transduction pathways in eukaryotic cells. Upon stimulation of phagocytic cells, Rac enhances the activity of the enzyme nicotinamide adenine dinucleotide phosphate (reduced) (NADPH) oxidase, resulting in the production of superoxide radicals. Activation of the NADPH oxidase requires the assembly of a multimolecular complex at the plasma membrane consisting of two integral membrane proteins, gp91(phox) and p2l(phox), and two cytosolic proteins, p67(phox) and p47(phox). Rac1 interacted directly with p67(phox) in GTP-dependent manner. Modified forms of Rac with mutations in the effector site did not stimulate oxidase activity or bind to p67(phox). Thus, p67(phox) appears to be the Rac effector protein in the NADPH oxidase complex.