Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes

@article{Liu1991CalcineurinIA,
  title={Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes},
  author={Jun Liu and Jesse D. Farmer and W. Lane and Jeff Friedman and Irving Weissman and Stuart L. Schreiber},
  journal={Cell},
  year={1991},
  volume={66},
  pages={807-815}
}
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… Expand

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TLDR
An identical spectrum of activities of FK506, CsA, rapamycin, and 506BD on IgE receptor-mediated signal transduction that results in exocytosis of secretory granules from the rat basophilic leukemia cell line RBL-2H3, a mast cell model suggests the existence of a common step in cytoplasmic signaling in T cells and mast cells. Expand
A cytosolic binding protein for the immunosuppressant FK506 has peptidyl-prolyl isomerase activity but is distinct from cyclophilin
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Findings pose serious questions concerning a direct role of cyclosporin in mediating CsA's immunosuppressive and nephrotoxic activities and raise doubts about whether PPIase has a direct function in lymphocyte signal transduction. Expand
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Using constructs in which mRNA production controlled by a specific transcription factor could be readily measured, it was found that both cyclosporin A and FK506 completely inhibited transcription activated by NF‐AT,NFIL2 A, NFIL2 B and partially inhibited transcriptionactivated by NF kappa B, indicating that only a subset of signalling pathways regulated by Ca2+ is sensitive to these drugs. Expand
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A receptor for the immuno-suppressant FK506 is a cis–trans peptidyl-prolyl isomerase
TLDR
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It is demonstrated that in the lower eukaryotes N. crassa and S. cerevisiae, cyclophilin mediates the cytotoxic CsA effect, which is similar to peptidyl-prolyl ds-trans isomerase, a novel type of enzyme that accelerates the slow refolding phase of certain proteins in vitro. Expand
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