Calcineurin mediates inhibition by FK506 and cyclosporin of recovery from alpha-factor arrest in yeast

Nature. 1992 Dec 17;360(6405):682-4. doi: 10.1038/360682a0.


The structurally unrelated immunosuppressants FK506 and cyclosporin A (CsA) act similarly, inhibiting a Ca(2+)-dependent signal required for interleukin-2 transcription and T-cell activation. Each drug binds to its cytosolic receptor, FKBP-12 and cyclophilin, respectively, and the drug-receptor complexes inhibit the Ca2+/calmodulin-dependent protein phosphatase, calcineurin. In yeast, calcineurin has been implicated in recovery from alpha-mating factor arrest. Here we show that FK506 bound to yeast FKBP-12 appears to form a complex with yeast calcineurin. Moreover, recovery from mating factor arrest is highly sensitive to FK506 or CsA, and this sensitivity requires the presence of FKBP-12 or cyclophilin, respectively. These results define a key physiological target of an FK506- and CsA-sensitive signal pathway in yeast, suggest a high degree of mechanistic conservation with mammalian cells, and indicate that further examination of the yeast system should provide insight into the same process in T cells.

MeSH terms

  • Alleles
  • Calcineurin
  • Calmodulin-Binding Proteins / genetics
  • Calmodulin-Binding Proteins / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cyclosporine / pharmacology*
  • DNA, Fungal / genetics
  • Genes, Fungal
  • Haploidy
  • Macromolecular Substances
  • Mating Factor
  • Peptides / genetics*
  • Pheromones / genetics
  • Phosphoprotein Phosphatases / genetics
  • Phosphoprotein Phosphatases / metabolism*
  • Polymerase Chain Reaction
  • Restriction Mapping
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / physiology*
  • Tacrolimus / pharmacology*
  • Tacrolimus Binding Proteins


  • Calmodulin-Binding Proteins
  • Carrier Proteins
  • DNA, Fungal
  • Macromolecular Substances
  • Peptides
  • Pheromones
  • Mating Factor
  • Cyclosporine
  • Calcineurin
  • Phosphoprotein Phosphatases
  • Tacrolimus Binding Proteins
  • Tacrolimus