Mitogen-Activated Protein Kinases and Reactive Oxygen Species: How Can ROS Activate MAPK Pathways?
Mitogen-Activated Protein Kinases and Reactive Oxygen Species: How Can ROS Activate MAPK Pathways?
复制标题
DOI：
10.1155/2011/792639
复制
发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Pae HO
中科院分区：
文献类型：
--
作者：
Son Y;Cheong YK;Kim NH;Chung HT;Kang DG;Pae HO
丝裂原活化蛋白激酶（MAPK）是丝氨酸-苏氨酸蛋白激酶，在从细胞表面到细胞核的信号转导中起主要作用。MAPK由生长因子调节的细胞外信号相关激酶（ERK）和应激激活的MAPK、c-jun NH 2-末端激酶（JNKs）和p38 MAPK组成，是由MAPK、MAPK激酶（MAP 2K）和MAPK激酶（MAP 3 K）组成的三激酶信号传导模块的一部分。MAP 3 K磷酸化MAP 2K，其继而激活MAPK。MAPK磷酸酶（MKP）识别MAPK中存在的TXY氨基酸基序，使MAPK去磷酸化和失活。已知MAPK途径不仅受受体配体相互作用的影响，而且受置于细胞上的不同应激源的影响。诱导MAPK途径潜在活化的一种类型的应激是由活性氧（ROS）引起的氧化应激。通常，细胞中ROS产生的增加导致ERK、JNK或p38 MAPK的激活，但ROS激活这些激酶的机制尚不清楚。MAPK信号蛋白的氧化修饰和MKPs的失活和/或降解可能为ROS激活MAPK通路提供了可能的机制，本文将对此进行综述。
Mitogen-activated protein kinases (MAPKs) are serine-threonine protein kinases that play the major role in signal transduction from the cell surface to the nucleus. MAPKs, which consist of growth factor-regulated extracellular signal-related kinases (ERKs), and the stress-activated MAPKs, c-jun NH2-terminal kinases (JNKs) and p38 MAPKs, are part of a three-kinase signaling module composed of the MAPK, an MAPK kinase (MAP2K) and an MAPK kinase (MAP3K). MAP3Ks phosphorylate MAP2Ks, which in turn activate MAPKs. MAPK phosphatases (MKPs), which recognize the TXY amino acid motif present in MAPKs, dephosphorylate and deactivate MAPKs. MAPK pathways are known to be influenced not only by receptor ligand interactions, but also by different stressors placed on the cell. One type of stress that induces potential activation of MAPK pathways is the oxidative stress caused by reactive oxygen species (ROS). Generally, increased ROS production in a cell leads to the activation of ERKs, JNKs, or p38 MAPKs, but the mechanisms by which ROS can activate these kinases are unclear. Oxidative modifications of MAPK signaling proteins and inactivation and/or degradation of MKPs may provide the plausible mechanisms for activation of MAPK pathways by ROS, which will be reviewed in this paper.