Interaction between ran1+ protein kinase and cAMP dependent protein kinase as negative regulators of fission yeast meiosis

EMBO J. 1991 Dec;10(12):3759-68.


In fission yeast, meiosis is initiated by transcriptional activation of the mei3+ gene under the combined influence of the four mating type genes. The mei3+ gene product acts as a meiotic inducer by binding to and inhibiting the ran1+ protein kinase. Inactivation of ran1+ kinase is both necessary and sufficient to allow meiotic differentiation. We describe a class of mutants which are unable to undergo both normal meiosis and meiosis induced by inactivation of ran1+. In addition to these defects, the cells are sterile and unable to enter stationary phase. We have determined that the mutants define two complementation groups, designated cgs1+ and cgs2+ (continues to grow in stationary). The wild type allele of each gene has been isolated and sequence analysis of cgs1+ shows that it encodes a protein homologous to the regulatory subunit of cyclic AMP dependent protein kinase (cAPK). Biochemical studies demonstrate that in cgs1-1 containing cells, cAPK activity is unregulated by cyclic AMP (cAMP). Sequence analysis of cgs2+ shows that the predicted protein it encodes shares homology with a phosphodiesterase from Dictyostelium discoideum and biochemical studies demonstrate that cells containing a mutant allele of cgs2+ have elevated levels of cAMP. Thus, both genes encode proteins that regulate the activity of cAPK. We have previously shown that cells overproducing ran1+ kinase are meiotically defective. Here, we provide direct evidence that the meiotic defect caused by either unregulated cAPK activity or unregulated ran1+ kinase activity is due to inability to induce transcription of the mei2+ gene, which is required for meiotic initiation. We propose that the switch from vegetative growth to meiosis in fission yeast requires inactivation of ran1+ kinase and is prevented by unregulated levels of cAPK.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Blotting, Northern
  • Cloning, Molecular
  • Cyclic AMP / metabolism*
  • DNA / genetics
  • Genes, Fungal
  • Genes, Mating Type, Fungal
  • Meiosis*
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Mutation
  • Plasmids
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • RNA, Fungal / genetics
  • Schizosaccharomyces / cytology*
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / physiology
  • Sequence Homology, Nucleic Acid
  • Spores, Fungal


  • RNA, Fungal
  • DNA
  • Cyclic AMP
  • Protein Kinases

Associated data

  • GENBANK/S60010
  • GENBANK/S60014
  • GENBANK/S60016
  • GENBANK/S64905
  • GENBANK/S64907
  • GENBANK/S70678
  • GENBANK/X60045
  • GENBANK/X60046
  • GENBANK/X60047
  • GENBANK/X60048