Mitogen-Activated Protein Kinases and Reactive Oxygen Species: How Can ROS Activate MAPK Pathways?

Abstract

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.

Artemisinin mimics calorie restriction to extend yeast lifespan via a dual-phase mode: a conclusion drawn from global transcriptome profiling

“…As indicated, Kss1/Fus3-encoded yeast MAPK is closely related to mammalian ERK-type kinases, which functions as a critical checkpoint for protein biosynthesis [34,35]. In other words, if MAPK is inactivated, protein biosynthesis should be suppressed [36]. After exposure of PME yeast cells to CR, ART, or H 2 O 2 , downregulation of MAPK pathway genes and ribosomal protein genes occurs, implying protein biosynthesis is hampered in PME yeast cells.…”

LX2343 alleviates cognitive impairments in AD model rats by inhibiting oxidative stress-induced neuronal apoptosis and tauopathy

“…Since intracellular ROS activate the mitogen-activated protein kinase (MAPK) pathway in the mediation of STZ-induced cell death [24,25] , we next investigated whether LX2343 has a regulatory effect on the MAPK pathway. The results demonstrated that incubating SH-SY5Y and primary neuronal cells with STZ for 4 h induced an ~2.5-fold increase in JNK and p38 phosphorylation compared with the controls (Figure 3A), whereas LX2343 treatment antagonized the STZ-induced increase in phosphorylated JNK, c-Jun, and p38 in both SH-SY5Y ( Figure 3B, 3C) and primary neuronal cells ( Figure 3D, 3E) but had no effects on ERK ( Figure 3A and 3F) or p53 (Figure 3F) in SH-SY5Y cells.…”

Tumor Progression Locus 2-dependent Oxidative Burst Drives Phosphorylation of Extracellular Signal-regulated Kinase during TLR3 and 9 Signaling

“…In addition, several studies have demonstrated that ROS can induce activation of MAP kinases, including ERK (29,30). Because both poly I:C and CpG are known inducers of ROS (31, 32), we tested the possibility that ERK was phosphorylated via a ROS-dependent mechanism in BMDMs stimulated with these ligands.…”