Localizing NADPH Oxidase–Derived ROS
Localizing NADPH Oxidase–Derived ROS
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DOI：
10.1126/stke.3492006re8
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发表时间：
2006-08
期刊：
影响因子：
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通讯作者：
M. Ushio-Fukai
中科院分区：
文献类型：
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作者：
M. Ushio-Fukai
活性氧（ROS）作为信号分子介导各种生物反应，包括细胞迁移，生长和基因表达。ROS是可扩散的短寿命分子。因此，将ROS信号定位在特定的亚细胞区室对于在受体激活后激活氧化还原信号传导事件是必不可少的。NADPH（烟酰胺腺嘌呤二核苷酸磷酸）氧化酶是血管系统中ROS的主要来源之一;它由催化亚基（Nox 1、Nox 2、Nox 3、Nox 4或Nox 5）、p22 phox、p47 phox、p67 phox和小的鸟苷三磷酸酶Rac 1组成。通过p47 phox与支架蛋白TRAF 4和WAVE 1的相互作用，将NADPH氧化酶靶向板状伪足和膜皱褶中的焦点复合物，提供了实现定向细胞迁移所需的局部ROS产生的机制。ROS被认为是激活蛋白酪氨酸磷酸酶，其集中在特定的亚细胞区室，从而建立一个正反馈系统，激活氧化还原信号通路，以促进细胞运动。此外，ROS的产生可以通过NADPH氧化酶与脂筏和小窝相关的信号平台以及与内体的相互作用来定位。还有证据表明，NADPH氧化酶存在于细胞核中，表明其参与氧化还原反应基因的表达。本文综述了NADPH氧化酶靶向离散的亚细胞区室作为一种机制，本地化的ROS和下游氧化还原信号事件，介导的各种细胞功能的激活。这篇STKE综述，有3个图和55篇引文，描述了在靶向或极化细胞运动中局部产生活性氧的证据。将NADPH（烟酰胺腺嘌呤二核苷酸磷酸）氧化酶靶向细胞的片状伪足和膜皱褶中的焦点复合物提供了实现局部ROS产生的机制。这种靶向通过NADPH氧化酶的p47 phox亚基与各种支架蛋白如TRAF 4和WAVE 1的相互作用来实现。ROS被认为是抑制蛋白酪氨酸磷酸酶，从而建立促进定向细胞迁移的正反馈系统。此外，ROS的产生可以通过NADPH氧化酶与脂筏和小窝相关的信号平台以及与内体和细胞核的相互作用来定位。这些机制可能解释了局部ROS如何激活离散信号通路。
Reactive oxygen species (ROS) function as signaling molecules to mediate various biological responses, including cell migration, growth, and gene expression. ROS are diffusible and short-lived molecules. Thus, localizing the ROS signal at the specific subcellular compartment is essential for activating redox signaling events after receptor activation. NADPH (nicotinamide adenine dinucleotide phosphate) oxidase is one of the major sources of ROS in vasculature; it consists of a catalytic subunit (Nox1, Nox2, Nox3, Nox4, or Nox5), p22phox, p47phox, p67phox, and the small guanosine triphosphatase Rac1. Targeting of NADPH oxidase to focal complexes in lamellipodia and membrane ruffles through the interaction of p47phox with the scaffold proteins TRAF4 and WAVE1 provides a mechanism for achieving localized ROS production, which is required for directed cell migration. ROS are believed to inactivate protein tyrosine phosphatases, which concentrate in specific subcellular compartments, thereby establishing a positive feedback system that activates redox signaling pathways to promote cell movement. Additionally, ROS production may be localized through interactions of NADPH oxidase with signaling platforms associated with lipid rafts and caveolae, as well as with endosomes. There is also evidence that NADPH oxidase is found in the nucleus, indicating its involvement in redox-responsive gene expression. This review focuses on targeting of NADPH oxidase to discrete subcellular compartments as a mechanism of localizing ROS and activation of downstream redox signaling events that mediate various cell functions. This STKE Review, with 3 figures and 55 citations, describes evidence for localized production of reactive oxygen species in targeted or polarized cell movement. Targeting of NADPH (nicotinamide adenine dinucleotide phosphate) oxidase to the focal complexes in lamellipodia and membrane ruffles of cells provides a mechanism for achieving localized ROS production. This targeting is achieved by the interaction of the p47phox subunit of the NADPH oxidase with various scaffold proteins such as TRAF4 and WAVE1. ROS are believed to inactivate protein tyrosine phosphatases, thereby establishing a positive feedback system that promotes directed cell migration. Additionally, ROS production may be localized through interactions of NADPH oxidase with signaling platforms associated with lipid rafts and caveolae, as well as with endosomes and the nucleus. These mechanisms may explain how localized ROS activate discrete signaling pathways.