A Constitutively Active and Nuclear Form of the MAP Kinase ERK2 Is Sufficient for Neurite Outgrowth and Cell Transformation

Curr Biol. 1998 Oct 22;8(21):1141-50. doi: 10.1016/s0960-9822(07)00485-x.

Abstract

Background: Mitogen-activated protein (MAP) kinases are ubiquitous components of many signal transduction pathways. Constitutively active variants have been isolated for every component of the extracellular-signal-regulated kinase 1 (ERK1) and ERK2 MAP kinase pathway except for the ERK itself.

Results: To create an activated ERK2 variant, we fused ERK2 to the low activity form of its upstream regulator, the MAP kinase kinase MEK1. The ERK2 in this fusion protein was active in the absence of extracellular signals. Expression of the fusion protein in mammalian cells did not activate endogenous ERK1 or ERK2. It was sufficient, however, to induce activation of the transcription factors Elk-1 and AP-1, neurite extension in PC12 cells in the absence of nerve growth factor, and foci of morphologically and growth-transformed NIH3T3 cells, if the fusion protein was localized to the nucleus. A cytoplasmic fusion protein was without effect.

Conclusions: Activation of ERK2 is sufficient to cause several transcriptional and phenotypic responses in mammalian cells. Nuclear localization of activated ERK2 is required to induce these events.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cell Line
  • Cell Line, Transformed
  • Cell Nucleus / enzymology
  • Cell Nucleus / physiology*
  • Codon
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Luciferases / biosynthesis
  • MAP Kinase Kinase 1
  • Mice
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinase Kinases*
  • Mitogen-Activated Protein Kinases*
  • Mutagenesis, Insertional
  • Mutagenesis, Site-Directed
  • Nerve Growth Factors / physiology
  • Neurites / physiology*
  • PC12 Cells
  • Phenotype
  • Point Mutation
  • Protein-Serine-Threonine Kinases / metabolism*
  • Protein-Tyrosine Kinases / metabolism*
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction
  • Transcription Factors / metabolism
  • Transcription, Genetic*
  • Transfection

Substances

  • Codon
  • Nerve Growth Factors
  • Recombinant Fusion Proteins
  • Transcription Factors
  • Luciferases
  • Protein-Tyrosine Kinases
  • Protein-Serine-Threonine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 1
  • MAP2K1 protein, human
  • Map2k1 protein, mouse
  • Mitogen-Activated Protein Kinase Kinases