MSK1 and MSK2 are required for the mitogen- and stress-induced phosphorylation of CREB and ATF1 in fibroblasts

Mol Cell Biol. 2002 Apr;22(8):2871-81. doi: 10.1128/MCB.22.8.2871-2881.2002.

Abstract

Using mouse knockouts for mitogen- and stress-activated protein kinase 1 (MSK1) and MSK2 and a double knockout of both MSK1 and MSK2, we show that these protein kinases are required for the stress-induced phosphorylation of transcription factors CREB and ATF1 in primary embryonic fibroblasts. In contrast mitogen-induced phosphorylation of CREB and ATF1 is greatly reduced but not totally abolished. The mitogen- and stress-induced phosphorylation of CREB at Ser133 has been linked to the transcription of several immediate early genes, including c-fos, junB, and egr1. The knockout of both MSK1 and MSK2 resulted in a 50% reduction in c-fos and junB gene transcription in response to anisomycin or UV-C radiation but only a small reduction in response to tetradecanoyl phorbol acetate or epidermal growth factor in fibroblasts. The transcription of egr1 in response to both mitogenic and stress stimuli, as well as stress-induced apoptosis, was unaffected in the MSK1/MSK2 double knockout.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 1
  • Animals
  • Apoptosis
  • Calcium-Calmodulin-Dependent Protein Kinases / deficiency*
  • Calcium-Calmodulin-Dependent Protein Kinases / genetics*
  • Calcium-Calmodulin-Dependent Protein Kinases / physiology
  • Cell Division
  • Cells, Cultured
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • DNA-Binding Proteins*
  • Enzyme Activation
  • Fibroblasts / metabolism
  • Genes, Immediate-Early
  • Mice
  • Mice, Knockout
  • Mitogen-Activated Protein Kinases / metabolism
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / deficiency*
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Serine-Threonine Kinases / physiology
  • Ribosomal Protein S6 Kinases, 90-kDa*
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Activating Transcription Factor 1
  • Atf1 protein, mouse
  • Cyclic AMP Response Element-Binding Protein
  • DNA-Binding Proteins
  • Transcription Factors
  • Protein-Serine-Threonine Kinases
  • Ribosomal Protein S6 Kinases, 90-kDa
  • Rps6ka4 protein, mouse
  • mitogen and stress-activated protein kinase 1
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases