Redox signaling and the MAP kinase pathways.
The mitogen-activated protein (MAP) kinases are a large family of proline-directed, serine/threonine kinases that require tyrosine and threonine phosphorylation of a TxY motif in the activation loop for activation through a phosphorylation cascade involving a MAPKKK, MAPKK and MAPK, often referred to as the MAP kinase module. Three separate such modules have been identified, based on the TxY motif of the MAP kinase and the dual-specificity kinases that strictly phosphorylate their specific TxY sequence. They are the extracellular signal regulated kinases (ERKs), c-jun N-terminal kinases (JNKs) and p38 MAPKs. The ERKs are mainly associated with proliferation and differentiation while the JNKs and p38MAP kinases regulate responses to cellular stresses. Redox homeostasis is critical for proper cellular function. While reactive oxygen species (ROS) and oxidative stress have been implicated in injury, a rapidly growing literature suggests that a transient increase in ROS levels is an important mediator of proliferation and results in activation of various signaling molecules and pathways, among which the MAP kinases. This review will summarize the role of ROS in MAP kinase activation in various systems, including in macrophages, cells of myeloid origin that play an essential role in inflammation and express a multi-component NADPH oxidase that catalyzes the receptor-regulated production of ROS.
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
Forman
Henry Jay
HJ
D000818:Animals; D004789:Enzyme Activation; D006801:Humans; D008264:Macrophages / Q000201:enzymology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010084:Oxidation-Reduction; D010766:Phosphorylation; D017382:Reactive Oxygen Species; D015398:Signal Transduction
D017382:Reactive Oxygen Species; D020928:Mitogen-Activated Protein Kinases