Abstract
Background:
The regulation of the immediate-early gene c-fos serves as a paradigm for signal-activated gene induction. Lysophosphatidic acid is a potent serum-borne mitogen able to induce c-fos.
Results:
Analysing the signalling events following stimulation of mouse embryonic stem cells with serum and lysophosphatidic acid, we show that the extracellular signal-regulated kinase (ERK) pathway is involved in mediating c-fos induction. We demonstrate that the ERK-activated kinase MSK1 is required for full c-fos promoter activation, as well as for the phosphorylation of cAMP-responsive element (CRE) binding proteins. We propose that MSK1 contributes to ERK-mediated c-fos promoter activation by targeting CRE binding proteins.
Conclusion:
These results show that MSK1 is an important ERK-activated mediator of mitogen-stimulated c-fos induction. In addition, they indicate that MSK1 could act through CRE binding proteins to achieve c-fos promoter activation. Thus, they further our understanding of the complex regulation of the model immediate-early gene c-fos.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line
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Cyclic AMP Response Element-Binding Protein / metabolism
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Embryo, Mammalian / cytology
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Embryo, Mammalian / enzymology
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Embryo, Mammalian / metabolism
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Lysophospholipids / metabolism*
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MAP Kinase Signaling System / physiology
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Mice
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Mice, Knockout
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Mitogen-Activated Protein Kinase 1 / physiology
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Mitogen-Activated Protein Kinases / physiology
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Phosphorylation
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Proto-Oncogene Proteins c-fos / metabolism*
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Proto-Oncogene Proteins c-fos / physiology
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Ribosomal Protein S6 Kinases, 90-kDa / deficiency
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Ribosomal Protein S6 Kinases, 90-kDa / physiology*
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Serum Response Element / physiology
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Serum Response Factor / deficiency
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Serum Response Factor / physiology
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Signal Transduction / physiology
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Stem Cells / enzymology
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Stem Cells / metabolism
Substances
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Cyclic AMP Response Element-Binding Protein
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Lysophospholipids
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Proto-Oncogene Proteins c-fos
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Serum Response Factor
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Ribosomal Protein S6 Kinases, 90-kDa
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mitogen and stress-activated protein kinase 1
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinases