A receptor for the immuno-suppressant FK506 is a cis–trans peptidyl-prolyl isomerase

@article{Harding1989ARF,
  title={A receptor for the immuno-suppressant FK506 is a cis–trans peptidyl-prolyl isomerase},
  author={Matthew W. Harding and Andrzej Galat and David E Uehling and Stuart L. Schreiber},
  journal={Nature},
  year={1989},
  volume={341},
  pages={758-760}
}
THE structurally novel macrolide FK506 (refs 1,2) has recently been demonstrated to have potent immunosuppressive activity3–7 at concentrations several hundredfold lower than cyclosporin A (CsA). Cyclosporin A, a cyclic peptide, has found widespread clinical use in the prevention of graft rejection following bone marrow and organ transplantation8. The mechanisms of immunosuppression mediated by FK506 and CsA appear to be remarkably similar, suggesting that these unrelated structures act on a… Expand
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References

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FK506: a novel immunosuppressive agent. Characteristics of binding and uptake by human lymphocytes.
TLDR
The characteristics and kinetics of cellular uptake and intracellular binding of FK506 by human peripheral blood lymphocytes are described and the similarities between FK505 and cyclosporine are delineated, implying that the mechanism of action for these two drugs may be similar. Expand
Peptidyl-prolyl cis-trans isomerase is the cyclosporin A-binding protein cyclophilin
TLDR
It is proposed that the peptidyl-prolyl cis-trans isomerizing activity of PPIase may be involved in events, such as those occurring early in T-cell activation, that are suppressed by cyclosporin A. Expand
Cyclophilin and peptidyl-prolyl cis-trans isomerase are probably identical proteins
TLDR
The results indicate that this enzyme is probably identical to cyclophilin, a recently discovered mammalian protein which binds tightly to cyclosporin A (CsA), which is thought to be linked to the immunosuppressive action of CsA. Expand
FK-506--how much potential?
TLDR
The immunological properties of FK-506 are reviewed, its potential in the light of the impact already made by CsA is assessed and its two agents can act synergistically both in vivo and in vitro. Expand
Cyclophilin: a specific cytosolic binding protein for cyclosporin A.
TLDR
Isolation of cyclophilin from the cytosol of thymocytes suggests that the immunosuppressive activity of cyclosporin A is mediated by an intracellular mechanism, not by a membrane-associated mechanism. Expand
Novel immunosuppressive agent, FK506. In vitro effects on the cloned T cell activation.
TLDR
Results indicate that the novel immunosuppressive agent, FK506, affects T cell activation with mechanisms similar to those of CsA but at considerably lower concentrations. Expand
Cyclophilin: distribution and variant properties in normal and neoplastic tissues.
TLDR
The broad tissue and phylogenetic distribution of CyP, its highly conserved structure, and its increased content after mitogenic stimulation suggest a fundamental role in cellular metabolism. Expand
EFFECT OF A NEW IMMUNOSUPPRESSIVE AGENT, FK506, ON HUMAN LYMPHOCYTE RESPONSES IN VITRO: I. Inhibition of Expression of Alloanticen‐Activated Suppressor Cells, As Well As Induction of Alloreactivity
TLDR
FK506 inhibited, in a dose-dependent fashion, both IL-2 receptor and transferrin receptor expression on the alloactivated lymphocytes--whereas this agent inhibited only incompletely both expression of both receptors on lymphocytes stimulated with PHA. Expand
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TLDR
Cyclophilin represents a new class of abundant, highly conserved cytosolic proteins that probably play an important role in the regulation of T lymphocyte activation and proliferation. Expand
Effect of a new immunosuppressive agent, FK506, on human lymphocyte responses in vitro. II. Inhibition of the production of IL-2 and gamma-IFN, but not B cell-stimulating factor 2.
TLDR
FK506 inhibited in a dose-dependent manner both interleukin 2 and gamma-interferon secretion of PBMC stimulated with PHA and could not inhibit the B cell-stimulating factor 2 (BSF-2) production ofPBMC, indicating the possibility that FK506 might spare the B Cell function. Expand
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