Reactive Oxygen Species in the Activation of MAP Kinases

There are three well-defined subgroups of mitogen-activated protein kinases (MAPKs): the extracellular signal-regulated kinases (ERKs), the c-Jun N-terminal kinases (JNKs), and the p38 MAPKs. Three subgroups of MAPKs are involved in both cell growth and cell death, and the tight regulation of these pathways, therefore, is paramount in determining cell fate. MAPK pathways have been shown to be activated not only by receptor ligand interactions but also by different stressors placed on the cell. MAPK phosphatases (MKPs) dephosphorylate and deactivate MAPKs. Reactive oxygen species (ROS), such as hydrogen peroxide, have been reported to activate ERKs, JNKs, and 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 chapter.