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| CALCINEURIN IS A COMMON TARGET OF CYCLOPHILIN-CYCLOSPORINE-A AND FKBP-FK506 COMPLEXES |
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| Author(s): LIU J, FARMER JD, LANE WS, FRIEDMAN J, WEISSMAN I, SCHREIBER SL |
| Source: CELL Volume: 66 Issue: 4 Pages: 807-815 Published: AUG 23 1991 |
| Times Cited: 2,549 References: 43 |
| Abstract: Although the immediate receptors (immunophilins) of the immunosuppressants cyclosporin A (CsA) and FK506 are distinct, their similar mechanisms of inhibition of cell signaling suggest that their associated immunophilin complexes interact with a common target. We report here that the complexes cyclophilin-CsA and FKBP-FK506 (but not cyclophilin, FKBP, FKBP-rapamycin, or FKBP-506BD) competitively bind to and inhibit the Ca2+- and calmodulin-dependent phosphatase calcineurin, although the binding and inhibition of calcineurin do not require calmodulin. These results suggest that calcineurin is involved in a common step associated with T cell receptor and IgE receptor signaling pathways and that cyclophilin and FKBP mediate the actions of CsA and FK506, respectively, by forming drug-dependent complexes with and altering the activity of calcineurin-calmodulin. |
| Document Type: Article |
| Language: English |
| Reprint Address: LIU, J (reprint author), HARVARD UNIV, DEPT CHEM, CAMBRIDGE, MA 02138 USA |
Addresses:
1. STANFORD UNIV, MED CTR, SCH MED, HOWARD HUGHES MED INST, DEPT PATHOL, STANFORD, CA 94305 USA
2. HARVARD UNIV, MICROCHEM FACIL, CAMBRIDGE, MA 02138 USA
3. STANFORD UNIV, MED CTR, SCH MED, HOWARD HUGHES MED INST, DEPT DEV BIOL, STANFORD, CA 94305 USA |
| Publisher: CELL PRESS, 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: GC745 |
| ISSN: 0092-8674 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |