This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hasel, K W Articles by Sutcliffe, J G Search for Related Content PubMed PubMed Citation Articles by Hasel, K W Articles by Sutcliffe, J G

An endoplasmic reticulum-specific cyclophilin.

Department of Molecular Biology, Research Institute of Scripps Clinic, La Jolla, California 92037.

ABSTRACT

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.

This article has been cited by other articles:

• Carlton, P. S., Gopalakrishnan, R., Gupta, A., Liston, B. W., Habib, S., Morse, M. A., Stoner, G. D. (2002). Piroxicam Is an Ineffective Inhibitor of N-Nitrosomethylbenzylamine-induced Tumorigenesis in the Rat Esophagus. Cancer Res. 62: 4376-4382 [Abstract] [Full Text]  
• Nagata, T., Kishi, H., Liu, Q. L., Yoshino, T., Matsuda, T., Jin, Z. X., Murayama, K., Tsukada, K., Muraguchi, A. (2000). Possible Involvement of Cyclophilin B and Caspase-Activated Deoxyribonuclease in the Induction of Chromosomal DNA Degradation in TCR-Stimulated Thymocytes. J. Immunol. 165: 4281-4289 [Abstract] [Full Text]  
• Cristiani, R., Fontanesi, G., Casini, G., Petrucci, C., Viollet, C., Bagnoli, P. (2000). Expression of Somatostatin Subtype 1 Receptor in the Rabbit Retina. IOVS 41: 3191-3199 [Abstract] [Full Text]  
• Wu, Q., Miller, R. H., Ransohoff, R. M., Robinson, S., Bu, J., Nishiyama, A. (2000). Elevated Levels of the Chemokine GRO-1 Correlate with Elevated Oligodendrocyte Progenitor Proliferation in the Jimpy Mutant. J. Neurosci. 20: 2609-2617 [Abstract] [Full Text]  
• Kanaki, T., Bujo, H., Hirayama, S., Ishii, I., Morisaki, N., Schneider, W. J., Saito, Y. (1999). Expression of LR11, a Mosaic LDL Receptor Family Member, Is Markedly Increased in Atherosclerotic Lesions. Arterioscler. Thromb. Vasc. Bio. 19: 2687-2695 [Abstract] [Full Text]  
• O'Hara, B. F., Watson, F. L., Srere, H. K., Kumar, H., Wiler, S. W., Welch, S. K., Bitting, L., Heller, H. C., Kilduff, T. S. (1999). Gene Expression in the Brain across the Hibernation Cycle. J. Neurosci. 19: 3781-3790 [Abstract] [Full Text]  
• Anderson, R. A., Joyce, C., Davis, M., Reagan, J. W., Clark, M., Shelness, G. S., Rudel, L. L. (1998). Identification of a Form of Acyl-CoA:Cholesterol Acyltransferase Specific to Liver and Intestine in Nonhuman Primates. J. Biol. Chem. 273: 26747-26754 [Abstract] [Full Text]  
• Vehaskari, V. M., Hempe, J. M., Manning, J., Aviles, D. H., Carmichael, M. C. (1998). Developmental regulation of ENaC subunit mRNA levels in rat kidney. Am. J. Physiol. Cell Physiol. 274: C1661-C1666 [Abstract] [Full Text]  
• Mortillaro, M. J., Berezney, R. (1998). Matrin CYP, an SR-rich Cyclophilin That Associates with the Nuclear Matrix and Splicing Factors. J. Biol. Chem. 273: 8183-8192 [Abstract] [Full Text]  
• Takaki, Y., Muta, T., Iwanaga, S. (1997). A Peptidyl-prolyl cis/trans-Isomerase (Cyclophilin G) in Regulated Secretory Granules. J. Biol. Chem. 272: 28615-28621 [Abstract] [Full Text]  
• Billich, A., Winkler, G., Aschauer, H., Rot, A., Peichl, P. (1997). Presence of Cyclophilin A in Synovial Fluids of Patients with Rheumatoid Arthritis. J. Exp. Med. 185: 975-980 [Abstract] [Full Text]  
• Smith, T., Ferreira, L. R., Hebert, C., Norris, K., Sauk, J. J. (1995). Hsp47 and Cyclophilin B Traverse the Endoplasmic Reticulum with Procollagen into Pre-Golgi Intermediate Vesicles. J. Biol. Chem. 270: 18323-18328 [Abstract] [Full Text]  
• Dutta, M., Delhi, P., Sinha, K. M., Banerjee, R., Datta, A. K. (2001). Lack of Abundance of Cytoplasmic Cyclosporin A-binding Protein Renders Free-living Leishmania donovani Resistant to Cyclosporin A. J. Biol. Chem. 276: 19294-19300 [Abstract] [Full Text]  
• Cebrian, C., Areste, C., Nicolas, A., Olive, P., Carceller, A., Piulats, J., Meseguer, A. (2001). Kidney Androgen-regulated Protein Interacts with Cyclophilin B and Reduces Cyclosporine A-mediated Toxicity in Proximal Tubule Cells. J. Biol. Chem. 276: 29410-29419 [Abstract] [Full Text]