Abstract
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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References
Sigal, N. H. & Dumont, F. J. A. Rev. Immun. 519–560 (1992).
Liu, J. et al. Cell 66, 807–815 (1991).
O'Keefe, S. J. et al. Nature 357, 692–694 (1992).
Clipstone, N. A. & Crabtree, G. R. Nature 357, 695–697 (1992).
Cyert, M. S. et al. Proc. natn. Acad. Sci. U.S.A. 88, 7376–7380 (1991).
Cyert, M. S. & Thorner, J. Molec. cell. Biol 12, 3460–3469 (1992).
Nielsen, J. B. et al. Proc. natn. Acad. Sci. U.S.A. 89, 7471–7475 (1992).
Liu, Y. et al. Molec. gen. Genet. 227, 52–59 (1991).
Kuno, T. et al. Biochem. biophys. Res. Commun. 180, 1159–1163 (1991).
Brizuela, L. et al. Molec. cell. Biol. 11, 4616–4626 (1991).
Tropschug, M. et al. Nature 342, 953–955 (1989).
Haendler, B. et al. Gene 83, 39–46 (1989).
Barnes, D. A. & Thorner, J. Molec. cell. Biol. 6, 2828–2838 (1986).
Handschumacher, R. E. et al. Science 226, 544–547 (1984).
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Poor, F., Parent, S., Morin, N. et al. Calcineurin mediates inhibition by FK506 and cyclosporin of recovery from α-factor arrest in yeast. Nature 360, 682–684 (1992). https://doi.org/10.1038/360682a0
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DOI: https://doi.org/10.1038/360682a0
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