Cancer Center Karolinska, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
J Biochem. 2011 Oct;150(4):345-56. doi: 10.1093/jb/mvr104. Epub 2011 Aug 19.
Oxidation of the catalytic cysteine of protein-tyrosine phosphatases (PTP), which leads to their reversible inactivation, has emerged as an important regulatory mechanism linking cellular tyrosine phosphorylation and signalling by reactive-oxygen or -nitrogen species (ROS, RNS). This review focuses on recent findings about the involved pathways, enzymes and biochemical mechanisms. Both the general cellular redox state and extracellular ligand-stimulated ROS production can cause PTP oxidation. Members of the PTP family differ in their intrinsic susceptibility to oxidation, and different types of oxidative modification of the PTP catalytic cysteine can occur. The role of PTP oxidation for physiological signalling processes as well as in different pathologies is described on the basis of well-investigated examples. Criteria to establish the causal involvement of PTP oxidation in a given process are proposed. A better understanding of mechanisms leading to selective PTP oxidation in a cellular context, and finding ways to pharmacologically modulate these pathways are important topics for future research.
蛋白质酪氨酸磷酸酶（PTP）催化半胱氨酸的氧化导致其可逆失活，这已成为连接细胞酪氨酸磷酸化和活性氧或氮物种（ROS、RNS）信号转导的重要调节机制。这篇综述主要关注最近关于相关途径、酶和生化机制的发现。细胞的一般氧化还原状态和细胞外配体刺激的 ROS 产生都可以导致 PTP 氧化。PTP 家族的成员在其对氧化的固有敏感性方面存在差异，并且 PTP 催化半胱氨酸可能会发生不同类型的氧化修饰。根据已充分研究的实例，描述了 PTP 氧化在生理信号转导过程以及不同病理中的作用。提出了确定 PTP 氧化在特定过程中因果关系的标准。在细胞环境中导致 PTP 选择性氧化的机制的更好理解，以及找到药理学调节这些途径的方法，是未来研究的重要课题。
