title: MSK1 is required for CREB phosphorylation in response to mitogens in mouse embryonic stem cells.
abstract: Mouse embryonic stem (ES) cells homozygous for disruption of the MSK1 gene had no detectable MSK1 activity. However, their activators (extracellular signal related kinase (ERK)1/ERK2) were stimulated normally in mitogen- and stress-activated protein kinase (MSK)1-/- and wild type cells in response to tetradecanoylphorbol acetate (TPA) and epidermal growth factor (EGF). TPA and EGF induced the phosphorylation of cyclic AMP-responsive element binding protein (CREB) at Ser-133 and ATF1 at Ser-63 in wild type cells and this was abolished by inhibition of the mitogen-activated protein kinase cascade. In contrast, the TPA- and EGF-induced phosphorylation of CREB/ATF1 was barely detectable in MSK1-/- cells. However, basal and forskolin-induced phosphorylation was similar, indicating that the MSK1 'knockout' did not prevent CREB phosphorylation by cyclic AMP-dependent protein kinase. Thus MSK1 is required for CREB and ATF1 phosphorylation after mitogenic stimulation of ES cells.
authors.affiliation: MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, Dow Street, Dundee DD1 5EH, UK. j.s.c.arthur@dundee.ac.uk
authors.forename: J S
authors.initials: JS
authors.lastname: Arthur
authors.forename: P
authors.initials: P
authors.lastname: Cohen
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D022202:Chromosomes, Artificial, Bacterial; D003001:Cloning, Molecular; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004622:Embryo, Mammalian; D004815:Epidermal Growth Factor / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D011506:Proteins; D011994:Recombinant Proteins / Q000378:metabolism; D015183:Restriction Mapping; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D011506:Proteins; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D000123:Acetyltransferases; C079238:alcohol O-acetyltransferase; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C116919:mitogen and stress-activated protein kinase 1; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate