A Cytosolic Binding Protein for the Immunosuppressant FK506 Has Peptidyl-Prolyl Isomerase Activity But Is Distinct from Cyclophilin
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 by 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.
MSU Digital Commons Citation
Siekierka, John; Hung, Shirley H.Y.; Poe, Martin; Lin, C. Shirley; and Sigal, Nolan H., "A Cytosolic Binding Protein for the Immunosuppressant FK506 Has Peptidyl-Prolyl Isomerase Activity But Is Distinct from Cyclophilin" (1989). Department of Chemistry and Biochemistry Faculty Scholarship and Creative Works. 102.