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The kinase MSK1 is required for induction of c-<Emphasis Type="Italic">fos</Emphasis> by lysophosphatidic acid in mouse embryonic stem cells
Authors:Sebastian?Schuck  Ana?Soloaga  Gerhard?Schratt  J?Simon?C?Arthur  Email author" target="_blank">Alfred?NordheimEmail author
Institution:1.Interfakult?res Institut für Zellbiologie, Abteilung Molekularbiologie,Universit?t Tübingen,Tübingen,Germany;2.Max-Planck-Institute of Molecular Cell Biology and Genetics,Dresden,Germany;3.Department of Biochemistry,MRC Protein Phosphorylation Unit, University of Dundee,Dundee,UK;4.Division of Neuroscience, Children's Hospital and Department of Neurobiology,Harvard Medical School,Boston,USA
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.
Keywords:
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