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Signal transduction by tumor necrosis factor mediated by JNK protein kinases
UMass Chan Affiliations
Program in Molecular MedicineDepartment of Cancer Biology
Department of Biochemistry and Molecular Biology
Document Type
Journal ArticlePublication Date
1994-12-01Keywords
Amino Acid SequenceAnimals
Base Sequence
Calcium-Calmodulin-Dependent Protein Kinases
Cercopithecus aethiops
Cloning, Molecular
Enzyme Activation
Genetic Complementation Test
Hela Cells
HumansJNK Mitogen-Activated Protein KinasesMitogen-Activated Protein Kinase 9*Mitogen-Activated Protein KinasesMolecular Sequence DataProtein BindingProtein KinasesProto-Oncogene Proteins c-jun*Saccharomyces cerevisiae ProteinsSequence AlignmentSequence Homology, Amino AcidSignal TransductionTumor Necrosis Factor-alphaUltraviolet RaysLife SciencesMedicine and Health Sciences
Metadata
Show full item recordAbstract
JNK protein kinases are distantly related to mitogen-activated protein kinases (ERKs) and are activated by dual phosphorylation on Tyr and Thr. The JNK protein kinase group includes the 46-kDa isoform JNK1. Here we describe the molecular cloning of a second member of the JNK group, the 55-kDa protein kinase JNK2. The activities of both JNK isoforms are markedly increased by exposure of cells to UV radiation. Furthermore, JNK protein kinase activation is observed in cells treated with tumor necrosis factor. Although both JNK isoforms phosphorylate the NH2-terminal activation domain of the transcription factor c-Jun, the activity of JNK2 was approximately 10-fold greater than that of JNK1. This difference in c-Jun phosphorylation correlates with increased binding of c-Jun to JNK2 compared with JNK1. The distinct in vitro biochemical properties of these JNK isoforms suggest that they may have different functions in vivo. Evidence in favor of this hypothesis was obtained from the observation that JNK1, but not JNK2, complements a defect in the expression of the mitogen-activated protein kinase HOG1 in the yeast Saccharomyces cerevisiae. Together, these data indicate a role for the JNK group of protein kinases in the signal transduction pathway initiated by proinflammatory cytokines and UV radiation.Source
Mol Cell Biol. 1994 Dec;14(12):8376-84.Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38593PubMed ID
7969172Related Resources
Link to Article in PubMedCollections
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