MSK1 is required for CREB phosphorylation in response to mitogens in mouse embryonic stem cells

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    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.
    Original languageEnglish
    Pages (from-to)44-48
    Number of pages5
    JournalFEBS Letters
    Volume482
    Issue number1-2
    DOIs
    Publication statusPublished - 29 Sep 2000

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    Keywords

    • Animals
    • Tetradecanoylphorbol Acetate
    • Calcium-Calmodulin-Dependent Protein Kinases
    • Recombinant Proteins
    • Epidermal Growth Factor
    • Chromosomes, Artificial, Bacterial
    • Mice
    • Cyclic AMP Response Element-Binding Protein
    • Cloning, Molecular
    • Mice, Knockout
    • Mice, Inbred Strains
    • Phosphorylation
    • Ribosomal Protein S6 Kinases, 90-kDa
    • Restriction Mapping
    • Acetyltransferases
    • Proteins
    • Mitogen-Activated Protein Kinase 3
    • Mitogen-Activated Protein Kinases
    • Mitogen-Activated Protein Kinase 1
    • Stem Cells
    • Embryo, Mammalian

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