Abstract
The ERK, JNK/SAPK and p38/RK MAP kinase subtypes (reviewed in [1]) are differentially activated in mammalian cells by various stimuli, which elicit induction of immediate-early (IE) genes, such as c-fos and c-jun (reviewed in [1-3]), as well as phosphorylation of histone H3 [4] and HMG-14 [5]. Anisomycin and UV radiation have been suggested to induce c-fos and c-jun transcription via JNK/SAPK-mediated phosphorylation of TCF (ternary complex factor), for c-fos induction [6-8], and c-Jun and/or ATF-2 for c-jun induction [9-11] [12,13]. We report here that anisomycin and ultraviolet radiation (UV) activate MAP kinase kinase-6 (MKK6) [14,15], p38/RK [16] [17,18] and MAPKAP kinase-2 (MAPKAP K-2) [17-19]. By using the p38/RK inhibitor SB 203580 [20,21], we show that activation of p38/RK and/or its downstream effectors are essential for anisomycin- and UV-stimulated c-fos/c-jun induction and histone H3/HMG-14 phosphorylation, whereas JNK/SAPK activation and phosphorylation of c-Jun and ATF-2 are insufficient for these responses.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Activating Transcription Factor 2
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Animals
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Anisomycin / pharmacology
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Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Cell Line
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Cyclic AMP Response Element-Binding Protein / metabolism*
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Enzyme Activation
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Enzyme Inhibitors / metabolism
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Enzyme Inhibitors / pharmacology
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Epidermal Growth Factor / pharmacology
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Imidazoles / metabolism
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Imidazoles / pharmacology
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JNK Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 4
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Mice
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Mice, Inbred C3H
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Mitogen-Activated Protein Kinase Kinases*
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Mitogen-Activated Protein Kinases*
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Phosphorylation
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Protein Kinase Inhibitors
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Protein Kinases / metabolism*
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Proto-Oncogene Proteins c-jun / genetics
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Proto-Oncogene Proteins c-jun / metabolism
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Pyridines / metabolism
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Pyridines / pharmacology
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RNA, Messenger / genetics
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Transcription Factors / metabolism*
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Ultraviolet Rays
Substances
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Activating Transcription Factor 2
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Atf2 protein, mouse
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Cyclic AMP Response Element-Binding Protein
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Enzyme Inhibitors
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Imidazoles
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Protein Kinase Inhibitors
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Proto-Oncogene Proteins c-jun
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Pyridines
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RNA, Messenger
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Transcription Factors
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Epidermal Growth Factor
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Anisomycin
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Protein Kinases
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Calcium-Calmodulin-Dependent Protein Kinases
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 4
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Mitogen-Activated Protein Kinase Kinases
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SB 203580