The cytosolic-binding protein for the immunosuppressant FK-506 is both a ubiquitous and highly conserved peptidyl-prolyl cis-trans isomerase.
We have recently isolated an abundant cytosolic protein from human T-cells which specifically binds the immunosuppressive agent, FK-506. The FK-506-binding protein (FKBP) is a member of a novel class of proteins possessing peptidyl-prolyl cis-trans isomerase activity. These proteins are believed to play an important role in accelerating the rate at which proteins fold into their native conformations. In the present study, we demonstrate that FKBP is not a lymphoid-specific protein, but is widely distributed and phylogenically conserved. FKBP, purified from three sources (a human T-lymphocyte cell line JURKAT, bovine calf thymus, and Saccharomyces cerevisiae) exhibit identical molecular weights, immunological cross-reactivities, and a high degree of NH2-terminal amino acid sequence homology. In addition, FKBP from all sources possesses peptidyl-prolyl cis-trans isomerase activity which can be specifically inhibited by FK-506. We conclude that FKBP may serve an important biological function in all eukaryotic cells.
Siekierka
J J
JJ
Department of Immunology Research, Merck, Sharp & Dohme Research Laboratories, Rahway, New Jersey 07065.
Wiederrecht
G
G
Greulich
H
H
Boulton
D
D
Hung
S H
SH
Cryan
J
J
Hodges
P J
PJ
Sigal
N H
NH
D000591:Amino Acid Isomerases / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D002417:Cattle; D002460:Cell Line; D003600:Cytosol / Q000201:enzymology; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism*; D008969:Molecular Sequence Data; D019696:Peptidylprolyl Isomerase; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D012689:Sequence Homology, Nucleic Acid; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology; D016559:Tacrolimus
D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D007166:Immunosuppressive Agents; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase; D016559:Tacrolimus