The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Calcineurin phosphatase activity in T lymphocytes is inhibited by FK 506 and cyclosporin A.
Open accessAbstract
The immunosuppressive agents cyclosporin A (CsA) and FK 506 bind to distinct families of intracellular proteins (immunophilins) termed cyclophilins and FK 506-binding proteins (FKBPs). Recently, it has been shown that, in vitro, the complexes of CsA-cyclophilin and FK 506-FKBP-12 bind to and inhibit the activity of calcineurin, a calcium-dependent serine/threonine phosphatase. We have investigated the effects of drug treatment on phosphatase activity in T lymphocytes. Calcineurin is expressed in T cells, and its activity can be measured in cell lysates. Both CsA and FK 506 specifically inhibit cellular calcineurin at drug concentrations that inhibit interleukin 2 production in activated T cells. Rapamycin, which binds to FKBPs but exhibits different biological activities than FK 506, has no effect on calcineurin activity. Furthermore, excess concentrations of rapamycin prevent the effects of FK 506, apparently by displacing FK 506 from FKBPs. These results show that calcineurin is a target of drug-immunophilin complexes in vivo and establish a physiological role for calcineurin in T-cell activation.
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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
Chemistry and Biology of the Immunophilins and Their Immunosuppressive Ligands
Schreiber, S. L. (1991) · Science · doi:10.1126/science.1702904 · Cited by 1,494
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Linsley, P. S., & Ledbetter, J. A. (1993) · Annual Review of Immunology · doi:10.1146/annurev.iy.11.040193.001203 · Cited by 1,298
Gases as biological messengers: nitric oxide and carbon monoxide in the brain
Dawson, T., & Snyder, S. (1994) · The Journal of Neuroscience · doi:10.1523/jneurosci.14-09-05147.1994 · Cited by 1,043
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Galluzzi, L., Bravo-San Pedro, J. M., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Alnemri, E. S., Altucci, L., Andrews, D., Annicchiarico-Petruzzelli, M., et al. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2014.137 · Cited by 1,002
Calcium Absorption Across Epithelia
Hoenderop, J. G. J., Nilius, B., & Bindels, R. J. M. (2005) · Physiological Reviews · doi:10.1152/physrev.00003.2004 · Cited by 936
Isolation of a Protein Target of the FKBP12-Rapamycin Complex in Mammalian Cells
Sabers, C. J., Martin, M. M., Brunn, G. J., Williams, J. M., Dumont, F. J., Wiederrecht, G., & Abraham, R. T. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.2.815 · Cited by 887
Metadata
- Authors
- Fruman, D. A., Klee, C. B., Bierer, B. E., & Burakoff, S. J.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1992-05
- Volume
- 89
- Issue
- 9
- Pages
- 3686-3690
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2018365938
- Cited by
- 823
- References
- 2
- FWCI
- 19.85
- Type
- journal article
- Language
- en
- Open access
- green
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- Fruman, D. A., Klee, C. B., Bierer, B. E., & Burakoff, S. J. (1992). Calcineurin phosphatase activity in T lymphocytes is inhibited by FK 506 and cyclosporin A. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.89.9.3686
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