Alternative splicing of Slo channel gene programmed by estrogen, progesterone and pregnancy.
Alternative splicing of Slo channel gene programmed by estrogen, progesterone and pregnancy.
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由雌激素、孕激素和妊娠编程的 Slo 通道基因的选择性剪接。
DOI：
10.1016/j.febslet.2005.07.069
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Toro,Ligia
中科院分区：
文献类型：
--
作者：
Zhu,Ning;Eghbali,Mansoureh;Helguera,Gustavo;Song,Min;Stefani,Enrico;Toro,Ligia
STREX选择性外显子在Slo通道上添加了一个磷酸化序列，可以将蛋白激酶A（PKA）的调节从兴奋性逆转为抑制性。由于怀孕开关Slo对PKA的反应从抑制性到兴奋性，我们假设STREX表达减少与怀孕和性激素的调节。与总rSlo不同，总rSlo在妊娠中期升高，在足月时降低，STREX转录物随着妊娠的进行逐渐降低，在足月时接近80%。雌激素模拟了STREX的下调，而雌激素受体拮抗剂ICI 182，780或孕酮（Pg）则相反。雌激素和前列腺素对STREX剪接的调节为妊娠时Slo PKA相关表型改变提供了一种机制。
STREX alternative-exon adds to Slo channel a phosphorylation sequence that can invert protein kinase A (PKA) regulation from excitatory to inhibitory. Because pregnancy switches Slo responsiveness to PKA from inhibitory to excitatory, we hypothesized that STREX expression diminishes with pregnancy and is regulated by sex hormones. Different from total-rSlo, which is elevated around mid-pregnancy and decreases at term, STREX transcripts progressively decreased with pregnancy near 80% at term. STREX downregulation was mimicked by estrogen, and opposed by estrogen-receptor antagonist ICI 182,780 or progesterone (Pg). The regulation of STREX splicing directed by estrogen and Pg provides a mechanism for Slo’s PKA-related phenotypic alteration with pregnancy.