Mitogen-activated protein kinase pathways in redox signaling.
It has been known for quite some time that proper cellular function requires tight control of the cellular redox state. In recent years, a growing body of literature has provided evidence of a role for reactive oxygen species (ROS) as important mediators of proliferation, acting as second messengers to modulate the activation of various signaling molecules and pathways. In contrast to high levels of ROS that may induce modifications that inhibit the activity of cellular components or result in damage, repair and cell death, the hypothesis that low levels of ROS, produced enzymatically and in a regulated fashion, are required participants of signaling pathways controlling essential cellular function is gaining grounds. The concept that ROS specifically target components of these pathways is only beginning to be examined. The mitogen-activated protein kinases (MAPK) are a large family of proline-directed, serine/threonine kinases that require tyrosine and threonine phosphorylation of a ThrXTyr motif in the activation loop for activation. Receptor-ligand interaction leads to activation of a phosphorylation cascade where the minimal module is formed by MAPK, MAPK kinase and MAPK kinase kinase. Four separate MAPK and activating cascades have been identified, based on the TXY motif and the dual-specificity kinases that strictly phosphorylate their particular TXY sequence. They are the extracellular signal regulated kinases (ERK), c-jun N-terminal kinases (JNK), p38MAPK and ERK5. This review will summarize recent findings regarding the activation of the MAPK and the role played by ROS in their activation.
Torres
Martine
M
Childrens Hospital Los Angeles Research Institute, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA. mtorres@chla.usc.edu
D000818:Animals; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D010084:Oxidation-Reduction
D020928:Mitogen-Activated Protein Kinases