A new first step in activation of steroid receptors -: Hormone-induced switching of FKBP51 and FKBP52 immunophilins
A new first step in activation of steroid receptors -: Hormone-induced switching of FKBP51 and FKBP52 immunophilins
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DOI：
10.1074/jbc.c100531200
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发表时间：
2002-02-15
影响因子：
4.8
通讯作者：
Sánchez, ER
中科院分区：
文献类型：
--
作者：
Davies, TH;Ning, YM;Sánchez, ER
我们已经确定了糖皮质激素受体(GR)激素激活的新的第一步。而不是导致细胞质GR异源复合体立即解离，激素诱导的一种免疫亲和素(FKBP51)替代另一种免疫亲和素(FKBP52)的结合，并伴随着运输蛋白dynein的招募，同时保持Hsp90不变。免疫荧光和分级显示激素诱导由激素产生的GR(.)HSP90(.)FKBP52(.)动力蛋白复合体从细胞质移位到细胞核，这一步骤先于细胞核内的复合体解离并将GR转化为DNA结合形式。总之，这些研究确认免疫亲和素交换是类固醇受体信号传递中最早的已知事件，并首次提供了FKBP51和FKBP52免疫亲和素在类固醇受体亚细胞定位和转运控制中的不同作用的证据。
We have identified a new first step in the hormonal activation of the glucocorticoid receptor (GR). Rather than causing immediate dissociation of the cytoplasmic GR heterocomplex, binding of hormone-induced substitution of one immunophilin (FKBP51) for another (FKBP52), and concomitant recruitment of the transport protein dynein while leaving Hsp90 unchanged. Immunofluorescence and fractionation revealed hormone-induced translocation of the hormone-generated GR(.)Hsp90(.)FKBP52(.)dynein complex from cytoplasm to nucleus, a step that precedes dissociation of the complex within the nucleus and conversion of GR to the DNA-binding form. Taken as a whole, these studies identify immunophilin interchange as the earliest known event in steroid receptor signaling and provide the first evidence of differential roles for FKBP51 and FKBP52 immunophilins in the control of steroid receptor subcellular localization and transport.