Authors
Dickens, MartinRogers, Jeffrey Scott
Cavanagh, Julie
Raitano, Art
Xia, Zhengui
Halpern, Jocelyn R.
Greenberg, Michael E.
Sawyers, Charles L.
Davis, Roger J.
UMass Chan Affiliations
Howard Hughes Medical Institute and Program in Molecular MedicineGraduate School of Biomedical Sciences
Document Type
Journal ArticlePublication Date
1997-08-01Keywords
Activating Transcription Factor 2; Animals; COS Cells; Calcium-Calmodulin-Dependent Protein Kinases; Carrier Proteins; Cell Nucleus; Cell Transformation, Neoplastic; Cells, Cultured; Cloning, Molecular; Cyclic AMP Response Element-Binding Protein; Cytoplasm; Fusion Proteins, bcr-abl; Gene Expression Regulation; JNK Mitogen-Activated Protein Kinases; Mitogen-Activated Protein Kinase 9; *Mitogen-Activated Protein Kinases; Molecular Sequence Data; Phosphorylation; Protein Kinases; Proto-Oncogene Proteins c-jun; Recombinant Fusion Proteins; *Signal Transduction; Trans-Activation (Genetics); Transcription Factors; TransfectionLife Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
The c-Jun amino-terminal kinase (JNK) is a member of the stress-activated group of mitogen-activated protein (MAP) kinases that are implicated in the control of cell growth. A murine cytoplasmic protein that binds specifically to JNK [the JNK interacting protein-1 (JIP-1)] was characterized and cloned. JIP-1 caused cytoplasmic retention of JNK and inhibition of JNK-regulated gene expression. In addition, JIP-1 suppressed the effects of the JNK signaling pathway on cellular proliferation, including transformation by the Bcr-Abl oncogene. This analysis identifies JIP-1 as a specific inhibitor of the JNK signal transduction pathway and establishes protein targeting as a mechanism that regulates signaling by stress-activated MAP kinases.Source
Science. 1997 Aug 1;277(5326):693-6.
DOI
10.1126/science.277.5326.693Permanent Link to this Item
http://hdl.handle.net/20.500.14038/33640PubMed ID
9235893Related Resources
ae974a485f413a2113503eed53cd6c53
10.1126/science.277.5326.693
Scopus Count
Collections
Related items
Showing items related by title, author, creator and subject.
-
A mammalian scaffold complex that selectively mediates MAP kinase activationWhitmarsh, Alan J.; Cavanagh, Julie; Tournier, Cathy; Yasuda, Jun; Davis, Roger J. (1998-09-11)The c-Jun NH2-terminal kinase (JNK) group of mitogen-activated protein (MAP) kinases is activated by the exposure of cells to multiple forms of stress. A putative scaffold protein was identified that interacts with multiple components of the JNK signaling pathway, including the mixed-lineage group of MAP kinase kinase kinases (MLK), the MAP kinase kinase MKK7, and the MAP kinase JNK. This scaffold protein selectively enhanced JNK activation by the MLK signaling pathway. These data establish that a mammalian scaffold protein can mediate activation of a MAP kinase signaling pathway.
-
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.
-
Selective activation of p38 mitogen-activated protein (MAP) kinase isoforms by the MAP kinase kinases MKK3 and MKK6Enslen, Herve; Raingeaud, Joel; Davis, Roger J. (1998-01-27)The cellular response to treatment with proinflammatory cytokines or exposure to environmental stress is mediated, in part, by the p38 group of mitogen-activated protein (MAP) kinases. We report the molecular cloning of a novel isoform of p38 MAP kinase, p38 beta 2. This p38 MAP kinase, like p38 alpha, is inhibited by the pyridinyl imidazole drug SB203580. The p38 MAP kinase kinase MKK6 is identified as a common activator of p38 alpha, p38 beta 2, and p38 gamma MAP kinase isoforms, while MKK3 activates only p38 alpha and p38 gamma MAP kinase isoforms. The MKK3 and MKK6 signal transduction pathways are therefore coupled to distinct, but overlapping, groups of p38 MAP kinases.