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

Abstract

CYCLOSPORIN A and the newly discovered immunosuppressant, FK-506, are potent inhibitors of T cell activation¹. 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^{1, 2}. The earliest responses inhibited in the T cell seem to be the expression of early phase T cell-activation genes for inter-leu kins 2, 3 and 4, granulocyte-macrophage colony stimulating factor and gamma interferon^2–4. Although FK-506 and cyclosporin A seem to inhibit similar signal transduction processes, they do so by interacting with distinct cytosolic proteins^{5, 6}. We report here the purification to homogeneity of a specific FK-506 binding protein that is distinct from the cyclosporin A-binding protein, cyclophilin^{7, 8}. In addition, we show that this FK-506 binding protein, like cyclophilin, has peptidyl-prolyl isomerase activity^{9, 10}.