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  • Title: Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes.
    Author: Liu J, Farmer JD, Lane WS, Friedman J, Weissman I, Schreiber SL.
    Journal: Cell; 1991 Aug 23; 66(4):807-15. PubMed ID: 1715244.
    Abstract:
    Although the immediate receptors (immunophilins) of the immunosuppressants cyclosporin A (CsA) and FK506 are distinct, their similar mechanisms of inhibition of cell signaling suggest that their associated immunophilin complexes interact with a common target. We report here that the complexes cyclophilin-CsA and FKBP-FK506 (but not cyclophilin, FKBP, FKBP-rapamycin, or FKBP-506BD) competitively bind to and inhibit the Ca(2+)- and calmodulin-dependent phosphatase calcineurin, although the binding and inhibition of calcineurin do not require calmodulin. These results suggest that calcineurin is involved in a common step associated with T cell receptor and IgE receptor signaling pathways and that cyclophilin and FKBP mediate the actions of CsA and FK506, respectively, by forming drug-dependent complexes with and altering the activity of calcineurin-calmodulin.
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