A cytosolic binding protein for the immunosuppressant FK506 has peptidyl-prolyl isomerase activity but is distinct from cyclophilin

Nature. 1989 Oct 26;341(6244):755-7. doi: 10.1038/341755a0.


CYCLOSPORIN A and the newly discovered immunosuppressant, FK-506, are potent inhibitors of T cell activation. In addition to their clinical importance in the prevention of allograft rejection, cyclosporin A and FK-506 represent important reagents for the study of the molecular mechanisms of lymphocyte activation. Cyclosporin A, a cyclic undecapeptide and FK-506, a macrolide, although chemically distinct, inhibit similar lymphocyte activation responses. The earliest responses inhibited in the T cell seem to be the expression of early phase T cell-activation genes for interleukins 2, 3 and 4, granulocyte-macrophage colony stimulating factor and gamma interferon. Although FK-506 and cyclosporin A seem to inhibit similar signal transduction processes, they do so be interacting with distinct cytosolic proteins. We report here the purification to homogeneity of a specific FK-506 binding protein that is distinct from the cyclosporin A-binding protein, cyclophilin. In addition, we show that this FK-506 binding protein, like cyclophilin, has peptidyl-prolyl isomerase activity.

MeSH terms

  • Amino Acid Isomerases / metabolism*
  • Animals
  • Anti-Bacterial Agents / metabolism*
  • Carrier Proteins / metabolism*
  • Cattle
  • Cyclosporins / metabolism
  • Cytosol / metabolism
  • Humans
  • Immunosuppressive Agents / metabolism*
  • Kinetics
  • Peptidylprolyl Isomerase
  • Radioligand Assay
  • Receptors, Immunologic / metabolism
  • T-Lymphocytes / enzymology
  • Tacrolimus


  • Anti-Bacterial Agents
  • Carrier Proteins
  • Cyclosporins
  • Immunosuppressive Agents
  • Receptors, Immunologic
  • Amino Acid Isomerases
  • Peptidylprolyl Isomerase
  • Tacrolimus