2 SIGNALS MEDIATE HORMONE-DEPENDENT NUCLEAR-LOCALIZATION OF THE GLUCOCORTICOID RECEPTOR

2 SIGNALS MEDIATE HORMONE-DEPENDENT NUCLEAR-LOCALIZATION OF THE GLUCOCORTICOID RECEPTOR
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DOI:
10.1002/j.1460-2075.1987.tb02654.x
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发表时间:
1987-11-01
期刊:
影响因子:
11.4
通讯作者:
YAMAMOTO, KR
YAMAMOTO, KR
中科院分区:
生物学1区
文献类型:
--
作者:
PICARD, D;YAMAMOTO, KR

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我们已经检测到795个氨基酸的大鼠糖皮质激素受体内的核定位信号。使用瞬时表达测定,我们通过免疫荧光监测受体衍生物和β-受体的亚细胞分布。半乳糖苷酶-受体融合蛋白。我们定义了两种不同的核定位信号,NL 1和NL 2。NL 1定位于与DNA结合结构域密切相关但不一致的28个氨基酸的区段; NL 2位于也包括激素结合结构域的256个氨基酸的区域内。最重要的是,核定位的融合蛋白含有全长受体或单独的NL 2区域是完全依赖于DNA的,获得了类似的结果与野生型受体,提供的分析是在培养基中进行缺乏血清和酚红。含NL 2的融合蛋白的表达诱导核定位的大鼠与受体介导的表达调节转录的快速动力学一致。因此,核定位的激素控制有助于糖皮质激素受体转录调节活性的调节。
We have detected nuclear localization signals within the 795 amino acid rat glucocorticoid receptor. Using a transient expression assay, we monitored by immunofluorescence the subcellular distribution of receptor derivatives and .beta.-galactosidase-receptor fusion proteins. Two distinct nuclear localization signals, NL1 and NL2, we defined. NL1 maps to a 28 amino acid segment closely associated, but not coincident with the DNA binding domain; NL2 resides within a 256 amino acid region that also includes the hormone binding domain. Most importantly, nuclear localization of fusion proteins containing either the full-length receptor or the NL2 region alone is fully hormone-dependent; similar results were obtained with the wild-type receptor, provided the analysis was performed in medium lacking serum and phenol red. The rat of hormone-induced nuclear localization of an NL2-containing fusion protein is consistent with the rapid kinetics of hormone-regulated transcription mediated by the receptor. Thus, hormonal control of nuclear localization contributes to the modulation of glucocorticoid receptor transcriptional regulatory activity.