The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Identification of the immunophilins capable of mediating inhibition of signal transduction by cyclosporin A and FK506: roles of calcineurin binding and cellular location.
Open accessAbstract
The immunosuppressants cyclosporin A (CsA) and FK506 appear to block T-cell function by inhibiting the calcium-regulated phosphatase calcineurin. While multiple distinct intracellular receptors for these drugs (cyclophilins and FKBPs, collectively immunophilins) have been characterized, the functionally active ones have not been discerned. We found that overexpression of cyclophilin A or B or FKBP12 increased T-cell sensitivity to CsA or FK506, respectively, demonstrating that they are able to mediate the inhibitory effects of their respective immunosuppressants in vivo. In contrast, cyclophilin C, FKBP13, and FKBP25 had no effect. Direct comparison of the Ki of each drug-immunophilin complex for calcineurin in vitro revealed that although calcineurin binding was clearly necessary, it was not sufficient to explain the in vivo activity of the immunophilin. Subcellular localization was shown also to play a role, since gene deletions of cyclophilins B and C which changed their intracellular locations altered their activities significantly. Cyclophilin B has been shown previously to be located within calcium-containing intracellular vesicles; its ability to mediate CsA inhibition implies that certain components of the signal transduction machinery are also spatially restricted within the cell.
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Cites
Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes
Liu, J., Farmer, J. D., Lane, W. S., Friedman, J., Weissman, I., & Schreiber, S. L. (1991) · Cell · doi:10.1016/0092-8674(91)90124-h · Cited by 4,116
Self-citationThe mechanism of action of cyclosporin A and FK506
Schreiber, S. L., & Crabtree, G. R. (1992) · Immunology Today · doi:10.1016/0167-5699(92)90111-j · Cited by 2,127
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FKBP51, a novel T-cell-specific immunophilin capable of calcineurin inhibition
Baughman, G., Wiederrecht, G. J., Campbell, N. F., Martin, M. M., & Bourgeois, S. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.8.4395 · Cited by 173
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Graef, I. A., Holsinger, L. J., Diver, S., Schreiber, S. L., & Crabtree, G. R. (1997) · The EMBO Journal · doi:10.1093/emboj/16.18.5618 · Cited by 67
Self-citationPeptidylprolylisomerases, Protein Folders, or Scaffolders? The Example of FKBP51 and FKBP52
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Patch testing and immunosuppression: a comprehensive review
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Metadata
- Authors
- Bram, R. J., Hung, D. T., Martin, P. K., Schreiber, S. L., & Crabtree, G. R.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 1993-08
- Volume
- 13
- Issue
- 8
- Pages
- 4760-4769
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W1842374849
- Cited by
- 277
- References
- 2
- FWCI
- 6.74
- Type
- journal article
- Language
- en
- Open access
- green
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