Schizosaccharomyces pombe cell division cycle under limited glucose requires Ssp1 kinase, the putative CaMKK, and Sds23, a PP2A-related phosphatase inhibitor

Genes Cells. 2009 May;14(5):539-54. doi: 10.1111/j.1365-2443.2009.01290.x. Epub 2009 Apr 15.

Abstract

Calcium/calmodulin-dependent protein kinase (CaMK) is required for diverse cellular functions, and similar kinases exist in fungi. Although mammalian CaMK kinase (CaMKK) activates CaMK and also evolutionarily-conserved AMP-activated protein kinase (AMPK), CaMKK is yet to be established in yeast. We here report that the fission yeast Schizosaccharomyces pombe Ssp1 kinase, which controls G2/M transition and response to stress, is the putative CaMKK. Ssp1 has a CaM binding domain (CBD) and associates with 14-3-3 proteins as mammalian CaMKK does. Temperature-sensitive ssp1 mutants isolated are defective in the tolerance to limited glucose, and this tolerance requires the conserved stretch present between the kinase domain and CBD. Sds23, multi-copy suppressor for mutants defective in type 1 phosphatase and APC/cyclosome, also suppresses the ssp1 phenotype, and is required for the tolerance to limited glucose. We demonstrate that Sds23 binds to type 2A protein phosphatases (PP2A) and PP2A-related phosphatase Ppe1, and that Sds23 inhibits Ppe1 phosphatase activity. Ssp1 and Ppe1 thus seem to antagonize in utilizing limited glucose. We also show that Ppk9 and Ssp2 are the catalytic subunits of AMPK and AMPK-related kinases, respectively, which bind to common beta-(Amk2) and gamma-(Cbs2) subunits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Amino Acid Sequence
  • Calcium-Calmodulin-Dependent Protein Kinase Kinase / genetics
  • Calcium-Calmodulin-Dependent Protein Kinase Kinase / metabolism*
  • Cell Cycle / drug effects*
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Division / drug effects
  • G2 Phase / drug effects
  • Glucose / pharmacology*
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism*
  • Molecular Sequence Data
  • Okadaic Acid / pharmacology
  • Phosphoprotein Phosphatases / chemistry
  • Phosphoprotein Phosphatases / metabolism
  • Phosphorylation
  • Protein Binding
  • Protein Phosphatase 2 / antagonists & inhibitors
  • Protein Phosphatase 2 / chemistry
  • Protein Phosphatase 2 / metabolism
  • Schizosaccharomyces / cytology*
  • Schizosaccharomyces / drug effects
  • Schizosaccharomyces / enzymology
  • Schizosaccharomyces / metabolism*
  • Schizosaccharomyces pombe Proteins / chemistry
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Suppression, Genetic
  • Temperature

Substances

  • Cell Cycle Proteins
  • HSP70 Heat-Shock Proteins
  • PSS1 protein, S pombe
  • Schizosaccharomyces pombe Proteins
  • Sds23 protein, S pombe
  • Okadaic Acid
  • Cbs2 protein, S pombe
  • Calcium-Calmodulin-Dependent Protein Kinase Kinase
  • AMP-Activated Protein Kinases
  • ppe1 protein, S pombe
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2
  • Glucose