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首页> 外文期刊>Molecular and Cellular Biology >Induction of the rat prodynorphin gene through Gs-coupled receptors may involve phosphorylation-dependent derepression and activation.
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Induction of the rat prodynorphin gene through Gs-coupled receptors may involve phosphorylation-dependent derepression and activation.

机译：通过Gs偶联受体诱导大鼠前强啡肽基因可能涉及磷酸化依赖性抑制和激活。

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摘要

Prodynorphin transcription is activated via Gs-coupled receptors through a cyclic AMP (cAMP)-dependent pathway. Four cAMP response elements (CREs) are present within the rat prodynorphin (RD) control region, and all four CREs appear to function in RD regulation. Three CREs located upstream between -1860 and -1504 are critical for receptor-responsive activity, but their function is distance dependent unless they act together with a fourth CRE found in exon 1. Regulation of RD also appears to involve multiple CRE-binding proteins. Both CRE-binding protein (CREB) and activator protein 1 (AP-1) can regulate RD, but their effects are in opposite directions; CREB represses and AP-1 activates RD. CREB-induced repression and AP-1 activation require distinct elements within the control region, but their binding and functions overlap at CRE-3. While CREB repression is dependent on CRE-3, AP-1 activation (and cAMP induction) of RD requires additional CREs (CRE-1, -2, and -4). CREB repression blocks AP-1 activation in unstimulated cells. However, phosphorylation relieves CREB-induced repression and enhances AP-1 activation. Gs-coupled receptor activation of RD may require phosphorylation-dependent derepression and activation steps.
机译：前强啡肽的转录通过依赖于环AMP（cAMP）的Gs偶联受体被激活。在大鼠强啡肽（RD）控制区内存在四个cAMP反应元件（CRE），并且所有四个CRE似乎在RD调节中起作用。位于-1860和-1504之间的上游的三个CRE对于受体响应活性至关重要，但除非与外显子1中的第四个CRE一起起作用，否则它们的功能是距离依赖性的。RD的调节似乎也涉及多个CRE结合蛋白。 CRE结合蛋白（CREB）和激活蛋白1（AP-1）均可调节RD，但其作用方向相反。 CREB抑制，AP-1激活RD。 CREB诱导的抑制和AP-1激活在控制区域内需要不同的元件，但它们的结合和功能在CRE-3上重叠。尽管CREB抑制取决于CRE-3，但RD的AP-1激活（和cAMP诱导）需要其他CRE（CRE-1，-2和-4）。 CREB抑制阻止未刺激细胞中AP-1的激活。但是，磷酸化可缓解CREB诱导的抑制并增强AP-1激活。 RD的Gs偶联受体激活可能需要依赖磷酸化的抑制和激活步骤。

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