| Title: | Calcineurin mediates inhibition by FK506 and cyclosporin of recovery from alpha-factor arrest in yeast |
| Author(s): | Foor F; Parent SA; Morin N; Dahl AM; Ramadan N; Chrebet G; Bostian KA; Nielsen JB; |
| Address: | "Merck Research Laboratories, Rahway, New Jersey 07065-0900" |
| ISSN/ISBN: | 0028-0836 (Print) 0028-0836 (Linking) |
| Abstract: | "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" |
| Keywords: | "Alleles Calcineurin Calmodulin-Binding Proteins/genetics/*metabolism Carrier Proteins/genetics/*metabolism Cyclosporine/*pharmacology DNA, Fungal/genetics Genes, Fungal Haploidy Macromolecular Substances Mating Factor Peptides/*genetics Pheromones/genetic;" |
| Notes: | "MedlineFoor, F Parent, S A Morin, N Dahl, A M Ramadan, N Chrebet, G Bostian, K A Nielsen, J B eng England 1992/12/17 Nature. 1992 Dec 17; 360(6405):682-4. doi: 10.1038/360682a0" |
