FK-506, a Potent Novel Immunosuppressive Agent, Binds to a Cytosolic Protein which is Distinct from the Cyclosporin a-Binding Protein, Cyclophilin
Document Type
Article
Publication Date
1-1-1989
Abstract
A novel macrolide antibiotic, FK-506, isolated from Streptomyces tsukubaensis, has been shown to be a potent immunosuppressive agent in vivo and in vitro. FK-506 shares a number of immunosuppressive properties with the cyclic peptide, cyclosporin A (CsA), although 10 to 100 times more potent in this regard. These similarities suggest that both agents may share a similar mechanism(s) of action at the biochemical level. We have identified a cytoplasmic binding protein for FK-506 in the human T cell line, JURKAT, using [3H]FK-506. The FK-506 binding protein has a m(R), of 10 to 12 kDa (as determined by gel filtration), is heat stable and does not bind CsA. This contrasts with the CsA binding protein, cyclophilin, in that cyclophilin is heat labile and has a m(R), of 15 to 17 kDa. Our data suggest that FK-506 binds to a low m.w. protein(s) in JURKAT cells, which is distinct from cyclophilin. This protein may mediate the immunosuppressive effects of FK-506 in T cells. In addition, our results suggest that the immunosuppressive activity of FK-506, as with CsA, is mediated by an intracellular mechanism.
Montclair State University Digital Commons Citation
Siekierka, John; Staruch, Mary Jo; Hung, Shirley H.Y.; and Sigal, Nolan H., "FK-506, a Potent Novel Immunosuppressive Agent, Binds to a Cytosolic Protein which is Distinct from the Cyclosporin a-Binding Protein, Cyclophilin" (1989). Department of Chemistry and Biochemistry Faculty Scholarship and Creative Works. 38.
https://digitalcommons.montclair.edu/chem-biochem-facpubs/38