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

FEBS Lett. 2000 Sep 29;482(1-2):44-8. doi: 10.1016/s0014-5793(00)02031-7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Cyclic AMP Response Element-Binding Protein
  • Proteins
  • Recombinant Proteins
  • Epidermal Growth Factor
  • Acetyltransferases
  • alcohol O-acetyltransferase
  • Ribosomal Protein S6 Kinases, 90-kDa
  • mitogen and stress-activated protein kinase 1
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • Tetradecanoylphorbol Acetate