MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway
UMass Chan AffiliationsHoward Hughes Medical Institute and Program in Molecular Medicine
KeywordsAmino Acid Sequence
Calcium-Calmodulin-Dependent Protein Kinases
*Gene Expression Regulation, Enzymologic
Gene Transfer Techniques
MAP Kinase Kinase 3
Mitogen-Activated Protein Kinase Kinases
*Mitogen-Activated Protein Kinases
Molecular Sequence Data
p38 Mitogen-Activated Protein Kinases
Medicine and Health Sciences
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AbstractThe p38 mitogen-activated protein (MAP) kinase signal transduction pathway is activated by proinflammatory cytokines and environmental stress. The detection of p38 MAP kinase in the nucleus of activated cells suggests that p38 MAP kinase can mediate signaling to the nucleus. To test this hypothesis, we constructed expression vectors for activated MKK3 and MKK6, two MAP kinase kinases that phosphorylate and activate p38 MAP kinase. Expression of activated MKK3 and MKK6 in cultured cells caused a selective increase in p38 MAP kinase activity. Cotransfection experiments demonstrated that p38 MAP kinase activation causes increased reporter gene expression mediated by the transcription factors ATF2 and Elk-1. These data demonstrate that the nucleus is one target of the p38 MAP kinase signal transduction pathway.
SourceMol Cell Biol. 1996 Mar;16(3):1247-55.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/38591
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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.
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