Stress-responsive protein kinases in redox-regulated apoptosis signaling.
Both extra- and intracellular stimuli elicit a wide variety of responses, such as cell survival, proliferation, differentiation, and apoptosis, through regulation of cell signaling. Recent studies have revealed that stress-responsive signal transduction pathways are strictly regulated by the intracellular redox state. The redox state of the cell is a consequence of the precise balance between the levels of oxidizing and reducing equivalents, such as reactive oxygen species (ROS) and endogenous antioxidants. The generation of ROS fluctuates in response to alterations of both external and internal environment and, in turn, triggers specific signaling cascades, including mitogen-activated protein kinases, which determine cell survival or cell death. This review focuses on the regulatory mechanisms of stress-responsive protein kinases and their involvement in oxidative stress-induced apoptosis. It also provides recent findings on the molecular mechanisms by which redox signaling cross-talks with stress-responsive protein kinase cascades.
Matsuzawa
Atsushi
A
Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Ichijo
Hidenori
H
D000818:Animals; D017209:Apoptosis; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011494:Protein Kinases / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction
D048848:MAP Kinase Kinase Kinase 5; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt