Activation of Srk1 by the mitogen-activated protein kinase Sty1/Spc1 precedes its dissociation from the kinase and signals its degradation

Mol Biol Cell. 2008 Apr;19(4):1670-9. doi: 10.1091/mbc.e07-07-0639. Epub 2008 Feb 13.

Abstract

Control of cell cycle progression by stress-activated protein kinases (SAPKs) is essential for cell adaptation to extracellular stimuli. The Schizosaccharomyces pombe SAPK Sty1/Spc1 orchestrates general changes in gene expression in response to diverse forms of cytotoxic stress. Here we show that Sty1/Spc1 is bound to its target, the Srk1 kinase, when the signaling pathway is inactive. In response to stress, Sty1/Spc1 phosphorylates Srk1 at threonine 463 of the regulatory domain, inducing both activation of Srk1 kinase, which negatively regulates cell cycle progression by inhibiting Cdc25, and dissociation of Srk1 from the SAPK, which leads to Srk1 degradation by the proteasome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Amino Acid Substitution
  • Cell Cycle / physiology
  • Cell Cycle Proteins / antagonists & inhibitors
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Enzyme Activation
  • Enzyme Stability
  • Fungal Proteins / antagonists & inhibitors
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Gene Expression Regulation, Fungal
  • MAP Kinase Signaling System
  • Mitogen-Activated Protein Kinases / chemistry
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism*
  • Models, Biological
  • Mutagenesis, Site-Directed
  • Phosphorylation
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Schizosaccharomyces / cytology
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / metabolism*
  • Schizosaccharomyces pombe Proteins / chemistry
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Signal Transduction
  • Threonine / chemistry
  • ras-GRF1 / antagonists & inhibitors
  • ras-GRF1 / genetics
  • ras-GRF1 / metabolism

Substances

  • Cell Cycle Proteins
  • Fungal Proteins
  • Recombinant Fusion Proteins
  • Schizosaccharomyces pombe Proteins
  • ras-GRF1
  • Threonine
  • SRK1 protein, S pombe
  • Mitogen-Activated Protein Kinases
  • Spc1 protein, S pombe
  • sty1 protein, S pombe
  • Proteasome Endopeptidase Complex