The kinase MSK1 is required for induction of c-fos by lysophosphatidic acid in mouse embryonic stem cells.
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.


CONCLUSIONS
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.
Schuck
Sebastian
S
Interfakultäres Institut für Zellbiologie, Abteilung Molekularbiologie, Universität Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany. schuck@mpi-cbg.de
Soloaga
Ana
A
Schratt
Gerhard
G
Arthur
J Simon C
JS
Nordheim
Alfred
A
D000818:Animals; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism* / Q000502:physiology; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000172:deficiency / Q000502:physiology*; D027602:Serum Response Element / Q000502:physiology; D026362:Serum Response Factor / Q000172:deficiency / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000201:enzymology / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; D008246:Lysophospholipids; D016760:Proto-Oncogene Proteins c-fos; D026362:Serum Response Factor; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C116919:mitogen and stress-activated protein kinase 1; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases