Protein Tyrosine Phosphatase regulation by Reactive Oxygen Species.

Advances in cancer research Pub Date : 2024-01-01 Epub Date: 2024-05-24 DOI:10.1016/bs.acr.2024.05.002
Colin L Welsh, Lalima K Madan
{"title":"Protein Tyrosine Phosphatase regulation by Reactive Oxygen Species.","authors":"Colin L Welsh, Lalima K Madan","doi":"10.1016/bs.acr.2024.05.002","DOIUrl":null,"url":null,"abstract":"<p><p>Protein Tyrosine Phosphatases (PTPs) help to maintain the balance of protein phosphorylation signals that drive cell division, proliferation, and differentiation. These enzymes are also well-suited to redox-dependent signaling and oxidative stress response due to their cysteine-based catalytic mechanism, which requires a deprotonated thiol group at the active site. This review focuses on PTP structural characteristics, active site chemical properties, and vulnerability to change by reactive oxygen species (ROS). PTPs can be oxidized and inactivated by H<sub>2</sub>O<sub>2</sub> through three non-exclusive mechanisms. These pathways are dependent on the coordinated actions of other H<sub>2</sub>O<sub>2</sub>-sensitive proteins, such as peroxidases like Peroxiredoxins (Prx) and Thioredoxins (Trx). PTPs undergo reversible oxidation by converting their active site cysteine from thiol to sulfenic acid. This sulfenic acid can then react with adjacent cysteines to form disulfide bonds or with nearby amides to form sulfenyl-amide linkages. Further oxidation of the sulfenic acid form to the sulfonic or sulfinic acid forms causes irreversible deactivation. Understanding the structural changes involved in both reversible and irreversible PTP oxidation can help with their chemical manipulation for therapeutic intervention. Nonetheless, more information remains unidentified than is presently known about the precise dynamics of proteins participating in oxidation events, as well as the specific oxidation states that can be targeted for PTPs. This review summarizes current information on PTP-specific oxidation patterns and explains how ROS-mediated signal transmission interacts with phosphorylation-based signaling machinery controlled by growth factor receptors and PTPs.</p>","PeriodicalId":94294,"journal":{"name":"Advances in cancer research","volume":"162 ","pages":"45-74"},"PeriodicalIF":0.0000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advances in cancer research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/bs.acr.2024.05.002","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/24 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Protein Tyrosine Phosphatases (PTPs) help to maintain the balance of protein phosphorylation signals that drive cell division, proliferation, and differentiation. These enzymes are also well-suited to redox-dependent signaling and oxidative stress response due to their cysteine-based catalytic mechanism, which requires a deprotonated thiol group at the active site. This review focuses on PTP structural characteristics, active site chemical properties, and vulnerability to change by reactive oxygen species (ROS). PTPs can be oxidized and inactivated by H2O2 through three non-exclusive mechanisms. These pathways are dependent on the coordinated actions of other H2O2-sensitive proteins, such as peroxidases like Peroxiredoxins (Prx) and Thioredoxins (Trx). PTPs undergo reversible oxidation by converting their active site cysteine from thiol to sulfenic acid. This sulfenic acid can then react with adjacent cysteines to form disulfide bonds or with nearby amides to form sulfenyl-amide linkages. Further oxidation of the sulfenic acid form to the sulfonic or sulfinic acid forms causes irreversible deactivation. Understanding the structural changes involved in both reversible and irreversible PTP oxidation can help with their chemical manipulation for therapeutic intervention. Nonetheless, more information remains unidentified than is presently known about the precise dynamics of proteins participating in oxidation events, as well as the specific oxidation states that can be targeted for PTPs. This review summarizes current information on PTP-specific oxidation patterns and explains how ROS-mediated signal transmission interacts with phosphorylation-based signaling machinery controlled by growth factor receptors and PTPs.

活性氧对蛋白酪氨酸磷酸酶的调控。
蛋白酪氨酸磷酸酶(PTPs)有助于维持驱动细胞分裂、增殖和分化的蛋白磷酸化信号的平衡。这些酶还非常适合氧化还原依赖性信号传导和氧化应激反应,因为它们的催化机制以半胱氨酸为基础,需要在活性位点有一个去质子化的硫醇基团。本综述将重点介绍 PTP 的结构特征、活性位点化学特性以及易受活性氧(ROS)影响的特性。PTP 可通过三种非排他性机制被 H2O2 氧化和灭活。这些途径依赖于其他对 H2O2 敏感的蛋白质的协调作用,如过氧化物酶,如过氧化还原酶(Peroxiredoxins,Prx)和硫氧还原酶(Thioredoxins,Trx)。PTPs 通过将其活性位点半胱氨酸从硫醇转化为亚硫酸来进行可逆氧化。然后,亚硫酸可与邻近的半胱氨酸反应形成二硫键,或与邻近的酰胺反应形成亚磺酰-酰胺连接。亚硫酸形式进一步氧化成磺酸或亚硫酸形式会导致不可逆的失活。了解可逆和不可逆 PTP 氧化过程中涉及的结构变化有助于对其进行化学处理,以进行治疗干预。然而,与目前已知的参与氧化事件的蛋白质的精确动态以及 PTPs 的特定氧化状态相比,还有更多的信息尚未确定。本综述总结了目前有关 PTP 特异氧化模式的信息,并解释了 ROS 介导的信号传输如何与生长因子受体和 PTP 控制的基于磷酸化的信号机制相互作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信