Abstract
Using mouse knockouts for mitogen- and stress-activated protein kinase 1 (MSK1) and MSK2 and a double knockout of both MSK1 and MSK2, we show that these protein kinases are required for the stress-induced phosphorylation of transcription factors CREB and ATF1 in primary embryonic fibroblasts. In contrast mitogen-induced phosphorylation of CREB and ATF1 is greatly reduced but not totally abolished. The mitogen- and stress-induced phosphorylation of CREB at Ser133 has been linked to the transcription of several immediate early genes, including c-fos, junB, and egr1. The knockout of both MSK1 and MSK2 resulted in a 50% reduction in c-fos and junB gene transcription in response to anisomycin or UV-C radiation but only a small reduction in response to tetradecanoyl phorbol acetate or epidermal growth factor in fibroblasts. The transcription of egr1 in response to both mitogenic and stress stimuli, as well as stress-induced apoptosis, was unaffected in the MSK1/MSK2 double knockout.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Activating Transcription Factor 1
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Animals
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Apoptosis
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Calcium-Calmodulin-Dependent Protein Kinases / deficiency*
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Calcium-Calmodulin-Dependent Protein Kinases / genetics*
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Calcium-Calmodulin-Dependent Protein Kinases / physiology
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Cell Division
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Cells, Cultured
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Cyclic AMP Response Element-Binding Protein / metabolism*
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DNA-Binding Proteins*
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Enzyme Activation
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Fibroblasts / metabolism
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Genes, Immediate-Early
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Mice
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Mice, Knockout
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Mitogen-Activated Protein Kinases / metabolism
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Phosphorylation
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Protein Serine-Threonine Kinases / deficiency*
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Protein Serine-Threonine Kinases / genetics*
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Protein Serine-Threonine Kinases / physiology
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Ribosomal Protein S6 Kinases, 90-kDa*
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Transcription Factors / metabolism*
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Transcription, Genetic
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p38 Mitogen-Activated Protein Kinases
Substances
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Activating Transcription Factor 1
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Atf1 protein, mouse
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Cyclic AMP Response Element-Binding Protein
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DNA-Binding Proteins
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Transcription Factors
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Protein Serine-Threonine Kinases
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Ribosomal Protein S6 Kinases, 90-kDa
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Rps6ka4 protein, mouse
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mitogen and stress-activated protein kinase 1
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Calcium-Calmodulin-Dependent Protein Kinases
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases