Signal transduction by tumor necrosis factor mediated by JNK protein kinases
UMass Chan AffiliationsProgram in Molecular Medicine
Department of Cancer Biology
Department of Biochemistry and Molecular Biology
Document TypeJournal Article
KeywordsAmino Acid Sequence
Calcium-Calmodulin-Dependent Protein Kinases
Genetic Complementation Test
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinase 9
*Mitogen-Activated Protein Kinases
Molecular Sequence Data
Proto-Oncogene Proteins c-jun
*Saccharomyces cerevisiae Proteins
Sequence Homology, Amino Acid
Tumor Necrosis Factor-alpha
Medicine and Health Sciences
MetadataShow full item record
AbstractJNK 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.
SourceMol Cell Biol. 1994 Dec;14(12):8376-84.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/38593
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Molecular determinants that mediate selective activation of p38 MAP kinase isoformsEnslen, Herve; Brancho, Deborah Marie; Davis, Roger J. (2000-03-16)The p38 mitogen-activated protein kinase (MAPK) group is represented by four isoforms in mammals (p38alpha, p38beta2, p38gamma and p38delta). These p38 MAPK isoforms appear to mediate distinct functions in vivo due, in part, to differences in substrate phosphorylation by individual p38 MAPKs and also to selective activation by MAPK kinases (MAPKKs). Here we report the identification of two factors that contribute to the specificity of p38 MAPK activation. One mechanism of specificity is the selective formation of functional complexes between MAPKK and different p38 MAPKs. The formation of these complexes requires the presence of a MAPK docking site in the N-terminus of the MAPKK. The second mechanism that confers signaling specificity is the selective recognition of the activation loop (T-loop) of p38 MAPK isoforms. Together, these processes provide a mechanism that enables the selective activation of p38 MAPK in response to activated MAPKK.
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