Zhu Ning, Eghbali Mansoureh, Helguera Gustavo, Song Min, Stefani Enrico, Toro Ligia
Department of Anesthesiology, Division of Molecular Medicine, University of California Los Angeles, Los Angeles, CA 90095-7115, USA.
FEBS Lett. 2005 Aug 29;579(21):4856-60. doi: 10.1016/j.febslet.2005.07.069.
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.
STREX可变外显子给Slo通道添加了一个磷酸化序列，该序列可将蛋白激酶A（PKA）的调节作用从兴奋性转变为抑制性。由于孕期会使Slo对PKA的反应性从抑制性转变为兴奋性，我们推测STREX的表达会随着孕期而减少且受性激素调节。与总rSlo不同，总rSlo在孕期中期左右升高并在足月时下降，而STREX转录本随着孕期逐渐减少，足月时接近80%。雌激素可模拟STREX的下调，而雌激素受体拮抗剂ICI 182,780或孕酮（Pg）则可对抗这种下调。雌激素和Pg对STREX剪接的调节为孕期Slo与PKA相关的表型改变提供了一种机制。
