Extracellular signal-dependent nuclear import of STAT3 is mediated by various importin alphas.
Extracellular signal-dependent nuclear import of STAT3 is mediated by various importin alphas.
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DOI：
10.1016/j.bbrc.2005.03.063
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发表时间：
2005-05
影响因子：
3.1
通讯作者：
R. Ushijima;Naoko Sakaguchi;Arihiro Kano;A. Maruyama;Y. Miyamoto;T. Sekimoto;Y. Yoneda;K. Ogino-K.-Ogin
中科院分区：
文献类型：
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作者：
R. Ushijima;Naoko Sakaguchi;Arihiro Kano;A. Maruyama;Y. Miyamoto;T. Sekimoto;Y. Yoneda;K. Ogino-K.-Ogin
信号转导子和转录激活子3（STAT 3）是一种参与多种生物学功能的转录因子。STAT 3通过酪氨酸残基的磷酸化、二聚化和随后的核转位被细胞因子和生长因子激活。然而，其核转位的机制尚不清楚。本文报道了一项关于精氨酸刺激的STAT 3输入细胞核的研究。首次在活细胞中建立了抑瘤素M（OSM）依赖的核输入分析系统。使用该系统，我们证明了显微注射importin α5/NPI-1突变体、抗importin β抗体和RanQ 69 L突变体抑制STAT 3的核输入。第二，我们发现酪氨酸磷酸化的STAT 3不仅与输入素α5/NPI-1相关，而且与其他输入素α相关，这是OSM刺激的结果，如溶液结合试验所证明的。这些结果表明，STAT 3的细胞外信号依赖性核转运是由各种importin αs，importin β和Ran介导的。
The signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is involved in a variety of biological functions. STAT3 is activated by cytokines and growth factors via the phosphorylation of a tyrosine residue, dimerization, and subsequent nuclear translocation. However, the mechanism of its nuclear translocation is unclear. A study of the cytokine-stimulated import of STAT3 into the nucleus is reported herein. An oncostatin M (OSM)-dependent nuclear import assay system was first established in living cells. Using this system, we demonstrated that the microinjection of the importin α5/NPI-1 mutant, an anti-importin β antibody, and the RanQ69L mutant inhibited the nuclear import of STAT3. Second, we showed that tyrosine-phosphorylated STAT3 associates, not only with importin α5/NPI-1 but also with other importin αs, as a result of OSM stimulation, as evidenced by a solution binding assay. These findings suggest that the extracellular signal-dependent nuclear transport of STAT3 is mediated by various importin αs, importin β, and Ran.