The MAPK kinase Pek1 acts as a phosphorylation-dependent molecular switch

Nature. 1999 Jun 3;399(6735):479-83. doi: 10.1038/20951.


The mitogen-activated protein kinase (MAPK) pathway is a highly conserved eukaryotic signalling cascade that converts extracellular signals into various outputs, such as cell growth and differentiation. MAPK is phosphorylated and activated by a specific MAPK kinase (MAPKK): MAPKK is therefore considered to be an activating regulator of MAPK. Pmk1 is a MAPK that regulates cell integrity and which, with calcineurin phosphatase, antagonizes chloride homeostasis in fission yeast. We have now identified Pek1, a MAPKK for Pmk1 MAPK. We show here that Pek1, in its unphosphorylated form, acts as a potent negative regulator of Pmk1 MAPK signalling. Mkh1, an upstream MAPKK kinase (MAPKKK), converts Pek1 from being an inhibitor to an activator. Our results indicate that Pek1 has a dual stimulatory and inhibitory function which depends on its phosphorylation state. This switch-like mechanism could contribute to the all-or-none physiological response mediated by the MAPK signalling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cell Cycle Proteins*
  • Enzyme Activation
  • Enzyme Inhibitors / metabolism
  • Fungal Proteins*
  • MAP Kinase Kinase 1*
  • Mitogen-Activated Protein Kinase Kinases
  • Mitogen-Activated Protein Kinases*
  • Molecular Sequence Data
  • Phosphorylases
  • Protein Kinases / metabolism*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Schizosaccharomyces / enzymology*
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces pombe Proteins
  • Sequence Homology, Amino Acid
  • Signal Transduction


  • Cell Cycle Proteins
  • Enzyme Inhibitors
  • Fungal Proteins
  • Schizosaccharomyces pombe Proteins
  • Phosphorylases
  • Protein Kinases
  • Mek1 protein, S pombe
  • Protein-Serine-Threonine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinases
  • Pmk1 protein, Magnaporthe grisea
  • MAP Kinase Kinase 1
  • Mitogen-Activated Protein Kinase Kinases

Associated data

  • GENBANK/D82023