Splicing potentiation by growth factor signals via estrogen receptor phosphorylation.
Splicing potentiation by growth factor signals via estrogen receptor phosphorylation.
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DOI：
10.1073/pnas.0503197102
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发表时间：
2005-06
影响因子：
11.1
通讯作者：
Y. Masuhiro;Y. Mezaki;Matomo Sakari;K. Takeyama;Tasuku Yoshida;Kunio Inoue;J. Yanagisawa;S. Hanazawa;B. O’Malley;S. Kato
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文献类型：
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作者：
Y. Masuhiro;Y. Mezaki;Matomo Sakari;K. Takeyama;Tasuku Yoshida;Kunio Inoue;J. Yanagisawa;S. Hanazawa;B. O’Malley;S. Kato
已知有丝分裂原激活的蛋白激酶介导的生长因子信号通过磷酸化er α n端转激活（激活功能-1）区域Ser-118，增强核雌激素受体α (er α)配体诱导的转激活功能。我们发现剪接体成分剪接因子（SF）3a p120是人类erα (herα)激活功能特异性的辅助激活因子-1，它依赖于Ser-118的磷酸化状态，与erα存在物理关联。SF3a p120增强了heralpha介导的RNA剪接，值得注意的是，SF3a p120增强RNA剪接依赖于hER Ser-118磷酸化。因此，我们的研究结果提示了一种机制，即生长因子信号可以通过序列特异性激活子的磷酸化来调节RNA剪接效率，从而在这些激活子与剪接体之间产生关联。
Mitogen-activated protein kinase-mediated growth factor signals are known to augment the ligand-induced transactivation function of nuclear estrogen receptor alpha (ERalpha) through phosphorylation of Ser-118 within the ERalpha N-terminal transactivation (activation function-1) domain. We identified the spliceosome component splicing factor (SF)3a p120 as a coactivator specific for human ERalpha (hERalpha) activation function-1 that physically associated with ERalpha dependent on the phosphorylation state of Ser-118. SF3a p120 potentiated hERalpha-mediated RNA splicing, and notably, the potentiation of RNA splicing by SF3a p120 depended on hER Ser-118 phosphorylation. Thus, our findings suggest a mechanism by which growth factor signaling can regulate gene expression through the modulation of RNA splicing efficiency via phosphorylation of sequence-specific activators, after association between such activators and the spliceosome.