Adenylate cyclase-coupled vasopressin receptor activates AQP2 promoter via a dual effect on CRE and AP1 elements.
Adenylate cyclase-coupled vasopressin receptor activates AQP2 promoter via a dual effect on CRE and AP1 elements.
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腺苷酸环化酶偶联的加压素受体通过对 CRE 和 AP1 元件的双重作用激活 AQP2 启动子。
DOI：
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发表时间：
1997
影响因子：
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通讯作者：
A. Aperia
中科院分区：
文献类型：
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作者：
M. Yasui;S. Zelenin;G. Celsi;A. Aperia
抗利尿激素通过激活集水管特异性水通道水通道蛋白-2 (AQP2)，在水平衡调节中起重要作用。在这里，我们提出的证据表明，抗利尿激素也可能作为AQP2的长期转录调节剂。这些研究是在通常表达V2受体（V2R）的LLC-PK1细胞上进行的，这些细胞被转染了人类AQP2启动子的片段。激活lc - pk1细胞中腺苷酸环化酶偶联的V2R可诱导腺苷3′，5′-环单磷酸腺苷（cAMP）响应元件结合蛋白（CREB）的磷酸化和c-Fos的表达。这些因子与CRE和AP1位点的结合确实联合导致AQP2启动子激活。这些结果确定了抗利尿激素作为转录调节剂的作用，并且是来自高度特异性受体的信息如何通过cAMP信号对CREB和直接早期基因表达的双重作用，转导到具有已知生物学效应的最终靶蛋白的转录的第一个例子。
Vasopressin plays an essential role for the regulation of water balance by activating the collecting duct-specific water channel, aquaporin-2 (AQP2). Here we present evidence that vasopressin may also act as a long-term, transcriptional regulator of AQP2. The studies were performed on LLC-PK1 cells, which normally express V2 receptor (V2R) and which were transfected with a fragment of the human AQP2 promoter. Activation of the adenylate cyclase-coupled V2R in LLC-PK1 cells induced phosphorylation of adenosine 3',5'-cyclic monophosphate (cAMP) responsive element binding protein (CREB) and expression of c-Fos. Binding of these factors to the CRE and AP1 site did, in combination, lead to AQP2 promoter activation. These results establish the role of vasopressin as a regulator of transcription and are the first example of how a message from a highly specific receptor is, via a dual effect of the cAMP signal on CREB and immediate early gene expression, transduced to the transcription of a final target protein with known biological effects.