CALCINEURIN IS A COMMON TARGET OF CYCLOPHILIN-CYCLOSPORINE-A AND FKBP-FK506 COMPLEXES
CALCINEURIN IS A COMMON TARGET OF CYCLOPHILIN-CYCLOSPORINE-A AND FKBP-FK506 COMPLEXES
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DOI：
10.1016/0092-8674(91)90124-h
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发表时间：
1991-08-23
期刊：
影响因子：
64.5
通讯作者：
SCHREIBER, SL
中科院分区：
文献类型：
--
作者：
LIU, J;FARMER, JD;SCHREIBER, SL
虽然免疫抑制剂环孢菌素A（CsA）和FK 506的直接受体（亲免素）是不同的，但它们抑制细胞信号传导的相似机制表明，它们相关的亲免素复合物与共同的靶标相互作用。我们在这里报告的复合物亲环素CsA和FKBP-FK 506（而不是亲环素，FKBP，FKBP-雷帕霉素，或FKBP-506 BD）竞争性结合和抑制钙离子和钙调蛋白依赖性磷酸酶钙调神经磷酸酶，虽然钙调神经磷酸酶的结合和抑制不需要钙调蛋白。这些结果表明，钙调神经磷酸酶参与了一个共同的步骤与T细胞受体和IgE受体信号通路，亲环素和FKBP介导的行动，CsA和FK 506，分别通过形成药物依赖性复合物，并改变活性的钙调神经磷酸酶钙调蛋白。
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.