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

• Published in: Nature (London) 1989-10, Vol.341 (6244), p.755-757
• Main Authors: Siekierka, John J, Hung, Shirley H. Y, Poe, Martin, Lin, C. Shirley, Sigal, Nolan H
• Format: Article
• Language: English
• Subjects: Amino Acid Isomerases - metabolism; Animals; Anti-Bacterial Agents - metabolism; Biology; Carrier Proteins - metabolism; Cattle; Cyclosporins - metabolism; Cytosol - metabolism; Enzymes; Homogeneity; Humans; Immunosuppressive Agents - metabolism; Kinetics; Lymphocytes; Peptidylprolyl Isomerase; Proteins; Radioligand Assay; Reagents; Receptors, Immunologic - metabolism; T-Lymphocytes - enzymology; Tacrolimus
• ISSN: 0028-0836; 1476-4687
• 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.