title: From JNK to pay dirt: jun kinases, their biochemistry, physiology and clinical importance.
abstract: The c-Jun N-terminal kinases (JNKs) were originally identified by their ability to phosphorylate c-Jun in response to UV-irradiation, but now are recognized as critical regulators of various aspects of mammalian physiology, including: cell proliferation, cell survival, cell death, DNA repair and metabolism. JNK-mediated phosphorylation enhances the ability of c-Jun, a component of the AP-1 transcription factor, to activate transcription, in response to a plethora of extracellular stimuli. The JNK activation leads to induction of AP-1-dependent target genes involved in cell proliferation, cell death, inflammation, and DNA repair. The JNKs, which are encoded by three different Jnk loci, are now known to be regulated by many other stimuli, from pro-inflammatory cytokines to obesity, in addition to UV-irradiation. Targeted disruption of the Jnk loci in mice has proved to be a critical tool in better understanding their physiological functions. Such studies revealed that the JNKs play important roles in numerous cellular processes, including: programmed cell death, T cell differentiation, negative regulation of insulin signaling, control of fat deposition, and epithelial sheet migration. Importantly, the JNKs have become prime targets for drug development in several important clinical areas, including: inflammation, diabetes, and cancer.
authors.affiliation: Department of Pharmacology, School of Medicine, University of California, San Diego, California 92093-0723, USA. karinoffice@ucsd.edu
authors.forename: Michael
authors.initials: M
authors.lastname: Karin
authors.forename: Ewen
authors.initials: E
authors.lastname: Gallagher
mesh_terms: D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D002454:Cell Differentiation; D002465:Cell Movement; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism; D004260:DNA Repair; D004847:Epithelial Cells / Q000166:cytology; D006801:Humans; D007249:Inflammation; D007328:Insulin / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*; D048670:MAP Kinase Kinase 4; D020935:MAP Kinase Signaling System; D051379:Mice; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D008957:Models, Genetic; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic; D014466:Ultraviolet Rays
chemical_list: D016207:Cytokines; D007328:Insulin; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D048031:JNK Mitogen-Activated Protein Kinases; D048055:Mitogen-Activated Protein Kinase 8; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases