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 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.
Siekierka
J J
JJ
Department of Immunology Research, Merck, Sharp and Dohme Research Laboratories, Rahway, New Jersey 07065.
Hung
S H
SH
Poe
M
M
Lin
C S
CS
Sigal
N H
NH
D000591:Amino Acid Isomerases / Q000378:metabolism*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D003524:Cyclosporins / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism*; D007700:Kinetics; D019696:Peptidylprolyl Isomerase; D011869:Radioligand Assay; D011971:Receptors, Immunologic / Q000378:metabolism; D013601:T-Lymphocytes / Q000201:enzymology; D016559:Tacrolimus
D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D003524:Cyclosporins; D007166:Immunosuppressive Agents; D011971:Receptors, Immunologic; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase; D016559:Tacrolimus