The extracellular signal-regulated protein kinases Erk1/Erk2 stimulate expression and biological activity of the transcriptional regulator Egr-1

Biol Chem. 2001 Jul;382(7):1077-81. doi: 10.1515/BC.2001.135.

Abstract

The zinc finger protein early growth response 1 (Egr-1) is a transcriptional activator involved in the regulation of growth and differentiation. We show here that a constitutive active mutant of mitogen-activated kinase kinase-1 (MAPKK-1) strongly stimulates the activity of the Egr-1 promoter, thus explaining the effects of mitogens upon Egr-1 mRNA and protein levels. Moreover, we show that a constitutive active MAPKK-1 leads to an increase in the biological activity of Egr-1 to activate transcription. We conclude that the signaling pathway involving mitogen-activated protein kinase/extracellular signal-regulated protein kinase has a dual impact on the biology of Egr-1 by controlling the transcription of the Egr-1 gene and the transcriptional activity of the Egr-1 protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / genetics
  • Early Growth Response Protein 1
  • Gene Expression Regulation*
  • Humans
  • Immediate-Early Proteins*
  • Luciferases / metabolism
  • MAP Kinase Kinase 1
  • MAP Kinase Signaling System*
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / physiology
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Mitogen-Activated Protein Kinase Kinases / physiology
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / physiology*
  • Mutagenesis, Site-Directed
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / physiology
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics
  • Transfection
  • beta-Galactosidase / genetics
  • beta-Galactosidase / metabolism

Substances

  • DNA-Binding Proteins
  • EGR1 protein, human
  • Early Growth Response Protein 1
  • Immediate-Early Proteins
  • Transcription Factors
  • Luciferases
  • Protein Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 1
  • MAP2K1 protein, human
  • Mitogen-Activated Protein Kinase Kinases
  • beta-Galactosidase