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nature portfolio permissions reprints privacy policy advertising ca2+/calmodulin-dependent protein phosphatase subscribe nature social media nature 357 nature 342 nature 360 nature ca2+-dependent signal required drug-receptor complexes inhibit α-mating factor arrest5 saccharomyces cerevisiae william personal data springerlink instant access csa-sensitive signal pathway data protection permissions privacy cmp2 protein phosphatases mating factor arrest α-factor arrest explore content subscription content european economic area key physiological target institutional subscriptions read bldg r80y-2a97 cch1-mid1 transporter accepting optional cookies calcineurin mediates inhibition journals search log issue learn t-cell activation1 article poor manage preferences article purchase yeast forrest poor content bostian & jennifer bostian  & jennifer access article cite nielsen rights yeast fkbp-12 appears https 1038/360682a0 journal publish

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         headline:Calcineurin mediates inhibition by FK506 and cyclosporin of recovery from α-factor arrest in yeast
         description:THE structurally unrelated immunosuppressants FK506 and cyclosporin A (CsA) act similarly, inhibiting a Ca2+-dependent signal required for interleukin-2 transcription and T-cell activation1. Each drug binds to its cytosolic receptor, FKBP-12 and cyclophilin, respectively, and the drug-receptor complexes inhibit the Ca2+/calmodulin-dependent protein phosphatase, calcineurin2–4. In yeast, calcineurin has been implicated in recovery from α-mating factor arrest5,6. 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.
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