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An endoplasmic reticulum-specific cyclophilin.
Department of Molecular Biology, Research Institute of Scripps Clinic, La Jolla, California 92037.
Cyclophilin is a ubiquitously expressed cytosolic peptidyl-prolyl cis-trans isomerase that is inhibited by the immunosuppressive drug cyclosporin A. A degenerate oligonucleotide based on a conserved cyclophilin sequence was used to isolate cDNA clones representing a ubiquitously expressed mRNA from mice and humans. This mRNA encodes a novel 20-kDa protein, CPH2, that shares 64% sequence identity with cyclophilin. Bacterially expressed CPH2 binds cyclosporin A and is a cyclosporin A-inhibitable peptidyl-prolyl cis-trans isomerase. Cell fractionation of rat liver followed by Western blot (immunoblot) analysis indicated that CPH2 is not cytosolic but rather is located exclusively in the endoplasmic reticulum. These results suggest that cyclosporin A mediates its effect on cells through more than one cyclophilin and that cyclosporin A-induced misfolding of T-cell membrane proteins normally mediated by CPH2 plays a role in immunosuppression.
PMID: 1710767 [PubMed - indexed for MEDLINE]
PMCID: PMC361082
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Cited by 23 PubMed Central articles
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Effect of troglitazone on plasma lipid metabolism and lipoprotein lipase.
Kobayashi J, Nagashima I, Hikita M, Bujo H, Takahashi K, Otabe M, Morisaki N, Saito Y.
Br J Clin Pharmacol. 1999 Apr; 47(4):433-9.
[Br J Clin Pharmacol. 1999]
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Involvement of two classes of binding sites in the interactions of cyclophilin B with peripheral blood T-lymphocytes.
Denys A, Allain F, Carpentier M, Spik G.
Biochem J. 1998 Dec 15; 336 ( Pt 3):689-97.
[Biochem J. 1998]
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Presence of cyclophilin A in synovial fluids of patients with rheumatoid arthritis.
Billich A, Winkler G, Aschauer H, Rot A, Peichl P.
J Exp Med. 1997 Mar 3; 185(5):975-80.
[J Exp Med. 1997]
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