Activation mechanism and physiological roles of stress-activated protein kinase/c-Jun NH2-terminal kinase in mammalian cells.
Stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK), which belongs to the family of mitogen-activated protein kinase (MAPK), is activated by many types of cellular stress or extracellular signals. Recent studies, including the analysis with knockout cells and mice, have led towards understanding the molecular mechanism of stress-induced SAPK/JNK activation and the physiological roles of SAPK/JNK in embryonic development and immune responses. Two SAPK/JNK activators, SEK1 and MKK7, are required for full activation of SAPK/JNK, which responds to various stimuli in an all-or-none manner in mouse embryonic stem (ES) cells. SAPK/JNK activation plays essential roles in organogenesis during mouse development by regulating cell proliferation, survival or apoptosis and in immune responses by regulating cytokine gene expression. Furthermore, SAPK/JNK is involved in regulation of mRNA stabilization, cell migration, and cytoskeletal integrity. Thus, SAPK/JNK has a wide range of functions in mammalian cells.
Nishina
H
H
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan. nishina@mol.f.u-tokyo.ac.jp
Nakagawa
K
K
Azuma
N
N
Katada
T
T
D000818:Animals; D017209:Apoptosis; D002465:Cell Movement; D003599:Cytoskeleton / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000166:cytology; D004789:Enzyme Activation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D008099:Liver / Q000378:metabolism; D048670:MAP Kinase Kinase 4; D048688:MAP Kinase Kinase 7; D051379:Mice; D018345:Mice, Knockout; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000737:chemistry* / Q000502:physiology*; D008954:Models, Biological; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism
D012333:RNA, Messenger; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D048688:MAP Kinase Kinase 7; C482559:MAP2K4 protein, human; C482569:MAP2K7 protein, human; C482562:Map2k4 protein, mouse; C482570:Map2k7 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases