Abstract
We report the protein purification and the cloning and characterization of a cDNA encoding the proteins that bind with high affinity to cyclophilin C (Cyp-C) in the absence of cyclosporin A. Transfection of this cDNA into COS cells directs the production of a glycoprotein of 77 kDa that binds to Cyp-C in the absence, but not the presence, of cyclosporin A. Homology comparisons reveal that this protein and gene, termed CyCAP for Cyp-C-associated protein, possess a cysteine-rich domain (scavenger receptor cysteine-rich domain) found in a variety of cell-surface molecules; the rest of the sequence is apparently specific. This result raises the possibility that Cyp-C serves as a mediator or regulator of an as-yet-unidentified signal or cellular process initiated via the Cyp-C-associated protein.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aruffo A., Melnick M. B., Linsley P. S., Seed B. The lymphocyte glycoprotein CD6 contains a repeated domain structure characteristic of a new family of cell surface and secreted proteins. J Exp Med. 1991 Oct 1;174(4):949–952. doi: 10.1084/jem.174.4.949. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bauw G., Van Damme J., Puype M., Vandekerckhove J., Gesser B., Ratz G. P., Lauridsen J. B., Celis J. E. Protein-electroblotting and -microsequencing strategies in generating protein data bases from two-dimensional gels. Proc Natl Acad Sci U S A. 1989 Oct;86(20):7701–7705. doi: 10.1073/pnas.86.20.7701. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bergsma D. J., Eder C., Gross M., Kersten H., Sylvester D., Appelbaum E., Cusimano D., Livi G. P., McLaughlin M. M., Kasyan K. The cyclophilin multigene family of peptidyl-prolyl isomerases. Characterization of three separate human isoforms. J Biol Chem. 1991 Dec 5;266(34):23204–23214. [PubMed] [Google Scholar]
- Callebaut I., Renoir J. M., Lebeau M. C., Massol N., Burny A., Baulieu E. E., Mornon J. P. An immunophilin that binds M(r) 90,000 heat shock protein: main structural features of a mammalian p59 protein. Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6270–6274. doi: 10.1073/pnas.89.14.6270. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clipstone N. A., Crabtree G. R. Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation. Nature. 1992 Jun 25;357(6380):695–697. doi: 10.1038/357695a0. [DOI] [PubMed] [Google Scholar]
- Dangott L. J., Jordan J. E., Bellet R. A., Garbers D. L. Cloning of the mRNA for the protein that crosslinks to the egg peptide speract. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2128–2132. doi: 10.1073/pnas.86.7.2128. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fischer G., Wittmann-Liebold B., Lang K., Kiefhaber T., Schmid F. X. Cyclophilin and peptidyl-prolyl cis-trans isomerase are probably identical proteins. Nature. 1989 Feb 2;337(6206):476–478. doi: 10.1038/337476a0. [DOI] [PubMed] [Google Scholar]
- Freeman M., Ashkenas J., Rees D. J., Kingsley D. M., Copeland N. G., Jenkins N. A., Krieger M. An ancient, highly conserved family of cysteine-rich protein domains revealed by cloning type I and type II murine macrophage scavenger receptors. Proc Natl Acad Sci U S A. 1990 Nov;87(22):8810–8814. doi: 10.1073/pnas.87.22.8810. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Friedman J., Weissman I. Two cytoplasmic candidates for immunophilin action are revealed by affinity for a new cyclophilin: one in the presence and one in the absence of CsA. Cell. 1991 Aug 23;66(4):799–806. doi: 10.1016/0092-8674(91)90123-g. [DOI] [PubMed] [Google Scholar]
- Fruman D. A., Klee C. B., Bierer B. E., Burakoff S. J. Calcineurin phosphatase activity in T lymphocytes is inhibited by FK 506 and cyclosporin A. Proc Natl Acad Sci U S A. 1992 May 1;89(9):3686–3690. doi: 10.1073/pnas.89.9.3686. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haendler B., Keller R., Hiestand P. C., Kocher H. P., Wegmann G., Movva N. R. Yeast cyclophilin: isolation and characterization of the protein, cDNA and gene. Gene. 1989 Nov 15;83(1):39–46. doi: 10.1016/0378-1119(89)90401-0. [DOI] [PubMed] [Google Scholar]
- Handschumacher R. E., Harding M. W., Rice J., Drugge R. J., Speicher D. W. Cyclophilin: a specific cytosolic binding protein for cyclosporin A. Science. 1984 Nov 2;226(4674):544–547. doi: 10.1126/science.6238408. [DOI] [PubMed] [Google Scholar]
- Hasel K. W., Glass J. R., Godbout M., Sutcliffe J. G. An endoplasmic reticulum-specific cyclophilin. Mol Cell Biol. 1991 Jul;11(7):3484–3491. doi: 10.1128/mcb.11.7.3484. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ke H. M., Zydowsky L. D., Liu J., Walsh C. T. Crystal structure of recombinant human T-cell cyclophilin A at 2.5 A resolution. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9483–9487. doi: 10.1073/pnas.88.21.9483. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ke H., Mayrose D., Cao W. Crystal structure of cyclophilin A complexed with substrate Ala-Pro suggests a solvent-assisted mechanism of cis-trans isomerization. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3324–3328. doi: 10.1073/pnas.90.8.3324. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kodama T., Freeman M., Rohrer L., Zabrecky J., Matsudaira P., Krieger M. Type I macrophage scavenger receptor contains alpha-helical and collagen-like coiled coils. Nature. 1990 Feb 8;343(6258):531–535. doi: 10.1038/343531a0. [DOI] [PubMed] [Google Scholar]
- Koser P. L., Sylvester D., Livi G. P., Bergsma D. J. A second cyclophilin-related gene in Saccharomyces cerevisiae. Nucleic Acids Res. 1990 Mar 25;18(6):1643–1643. doi: 10.1093/nar/18.6.1643. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LeGendre N. Immobilon-P transfer membrane: applications and utility in protein biochemical analysis. Biotechniques. 1990 Dec;9(6 Suppl):788–805. [PubMed] [Google Scholar]
- Liu J., Albers M. W., Wandless T. J., Luan S., Alberg D. G., Belshaw P. J., Cohen P., MacKintosh C., Klee C. B., Schreiber S. L. Inhibition of T cell signaling by immunophilin-ligand complexes correlates with loss of calcineurin phosphatase activity. Biochemistry. 1992 Apr 28;31(16):3896–3901. doi: 10.1021/bi00131a002. [DOI] [PubMed] [Google Scholar]
- Liu J., Farmer J. D., Jr, Lane W. S., Friedman J., Weissman I., Schreiber S. L. Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. Cell. 1991 Aug 23;66(4):807–815. doi: 10.1016/0092-8674(91)90124-h. [DOI] [PubMed] [Google Scholar]
- Matsumoto A., Naito M., Itakura H., Ikemoto S., Asaoka H., Hayakawa I., Kanamori H., Aburatani H., Takaku F., Suzuki H. Human macrophage scavenger receptors: primary structure, expression, and localization in atherosclerotic lesions. Proc Natl Acad Sci U S A. 1990 Dec;87(23):9133–9137. doi: 10.1073/pnas.87.23.9133. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Keefe S. J., Tamura J., Kincaid R. L., Tocci M. J., O'Neill E. A. FK-506- and CsA-sensitive activation of the interleukin-2 promoter by calcineurin. Nature. 1992 Jun 25;357(6380):692–694. doi: 10.1038/357692a0. [DOI] [PubMed] [Google Scholar]
- Ondek B., Hardy R. W., Baker E. K., Stamnes M. A., Shieh B. H., Zuker C. S. Genetic dissection of cyclophilin function. Saturation mutagenesis of the Drosophila cyclophilin homolog ninaA. J Biol Chem. 1992 Aug 15;267(23):16460–16466. [PubMed] [Google Scholar]
- Price E. R., Zydowsky L. D., Jin M. J., Baker C. H., McKeon F. D., Walsh C. T. Human cyclophilin B: a second cyclophilin gene encodes a peptidyl-prolyl isomerase with a signal sequence. Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1903–1907. doi: 10.1073/pnas.88.5.1903. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rohrer L., Freeman M., Kodama T., Penman M., Krieger M. Coiled-coil fibrous domains mediate ligand binding by macrophage scavenger receptor type II. Nature. 1990 Feb 8;343(6258):570–572. doi: 10.1038/343570a0. [DOI] [PubMed] [Google Scholar]
- Rubenstein J. L., Brice A. E., Ciaranello R. D., Denney D., Porteus M. H., Usdin T. B. Subtractive hybridization system using single-stranded phagemids with directional inserts. Nucleic Acids Res. 1990 Aug 25;18(16):4833–4842. doi: 10.1093/nar/18.16.4833. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saiki R. K., Scharf S., Faloona F., Mullis K. B., Horn G. T., Erlich H. A., Arnheim N. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science. 1985 Dec 20;230(4732):1350–1354. doi: 10.1126/science.2999980. [DOI] [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schneuwly S., Shortridge R. D., Larrivee D. C., Ono T., Ozaki M., Pak W. L. Drosophila ninaA gene encodes an eye-specific cyclophilin (cyclosporine A binding protein). Proc Natl Acad Sci U S A. 1989 Jul;86(14):5390–5394. doi: 10.1073/pnas.86.14.5390. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schreiber S. L. Immunophilin-sensitive protein phosphatase action in cell signaling pathways. Cell. 1992 Aug 7;70(3):365–368. doi: 10.1016/0092-8674(92)90158-9. [DOI] [PubMed] [Google Scholar]
- Shieh B. H., Stamnes M. A., Seavello S., Harris G. L., Zuker C. S. The ninaA gene required for visual transduction in Drosophila encodes a homologue of cyclosporin A-binding protein. Nature. 1989 Mar 2;338(6210):67–70. doi: 10.1038/338067a0. [DOI] [PubMed] [Google Scholar]
- Stamnes M. A., Shieh B. H., Chuman L., Harris G. L., Zuker C. S. The cyclophilin homolog ninaA is a tissue-specific integral membrane protein required for the proper synthesis of a subset of Drosophila rhodopsins. Cell. 1991 Apr 19;65(2):219–227. doi: 10.1016/0092-8674(91)90156-s. [DOI] [PubMed] [Google Scholar]
- Stone R. Molecular 'surgery' for brain tumors. Science. 1992 Jun 12;256(5063):1513–1513. doi: 10.1126/science.1317967. [DOI] [PubMed] [Google Scholar]
- Swanson S. K., Born T., Zydowsky L. D., Cho H., Chang H. Y., Walsh C. T., Rusnak F. Cyclosporin-mediated inhibition of bovine calcineurin by cyclophilins A and B. Proc Natl Acad Sci U S A. 1992 May 1;89(9):3741–3745. doi: 10.1073/pnas.89.9.3741. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Takahashi N., Hayano T., Suzuki M. Peptidyl-prolyl cis-trans isomerase is the cyclosporin A-binding protein cyclophilin. Nature. 1989 Feb 2;337(6206):473–475. doi: 10.1038/337473a0. [DOI] [PubMed] [Google Scholar]
- Takebe Y., Seiki M., Fujisawa J., Hoy P., Yokota K., Arai K., Yoshida M., Arai N. SR alpha promoter: an efficient and versatile mammalian cDNA expression system composed of the simian virus 40 early promoter and the R-U5 segment of human T-cell leukemia virus type 1 long terminal repeat. Mol Cell Biol. 1988 Jan;8(1):466–472. doi: 10.1128/mcb.8.1.466. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thériault Y., Logan T. M., Meadows R., Yu L., Olejniczak E. T., Holzman T. F., Simmer R. L., Fesik S. W. Solution structure of the cyclosporin A/cyclophilin complex by NMR. Nature. 1993 Jan 7;361(6407):88–91. doi: 10.1038/361088a0. [DOI] [PubMed] [Google Scholar]
- Tropschug M., Nicholson D. W., Hartl F. U., Köhler H., Pfanner N., Wachter E., Neupert W. Cyclosporin A-binding protein (cyclophilin) of Neurospora crassa. One gene codes for both the cytosolic and mitochondrial forms. J Biol Chem. 1988 Oct 5;263(28):14433–14440. [PubMed] [Google Scholar]
- Wijngaard P. L., Metzelaar M. J., MacHugh N. D., Morrison W. I., Clevers H. C. Molecular characterization of the WC1 antigen expressed specifically on bovine CD4-CD8- gamma delta T lymphocytes. J Immunol. 1992 Nov 15;149(10):3273–3277. [PubMed] [Google Scholar]
- Xu Q., Leiva M. C., Fischkoff S. A., Handschumacher R. E., Lyttle C. R. Leukocyte chemotactic activity of cyclophilin. J Biol Chem. 1992 Jun 15;267(17):11968–11971. [PubMed] [Google Scholar]
- Yuen S. W., Chui A. H., Wilson K. J., Yuan P. M. Microanalysis of SDS-PAGE electroblotted proteins. Biotechniques. 1989 Jan;7(1):74–83. [PubMed] [Google Scholar]