Transcriptional regulation of the human PRL-releasing peptide (PrRP) receptor gene by a dopamine 2 Receptor agonist: cloning and characterization of the human PrRP receptor gene and its promoter region.
Transcriptional regulation of the human PRL-releasing peptide (PrRP) receptor gene by a dopamine 2 Receptor agonist: cloning and characterization of the human PrRP receptor gene and its promoter region.
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多巴胺 2 受体激动剂对人 PRL 释放肽 (PrRP) 受体基因的转录调节：人 PrRP 受体基因及其启动子区域的克隆和表征。
DOI：
10.1210/mend.16.4.0819
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发表时间：
2002
影响因子：
--
通讯作者：
M. Mori
中科院分区：
文献类型：
--
作者：
A. Ozawa;M. Yamada;T. Satoh;T. Monden;K. Hashimoto;H. Kohga;Y. Hashiba;Tomio Sasaki;M. Mori
PRL释放肽受体（PrRPR）mRNA在垂体腺瘤中表达，但在用溴隐亭（多巴胺2（D2）受体的特异性激动剂）治疗的患者中未检测到。虽然溴隐亭治疗垂体腺瘤有效，但对D2受体介导的基因调控的分子机制知之甚少。所克隆的人PrRPR基因全长约2.0kb，含有两个外显子和一个内含子。两个功能性多聚腺苷酸化信号位于终止密码子下游510和714 bp处。引物延伸分析表明，在翻译起始位点上游139和140 bp处有两个主要的转录起始位点，在-161处有一个额外的次要位点。启动子区含有几个转录因子的结合位点，包括垂体特异性转录因子（Pit 1），激活蛋白1（AP-1）和特异性蛋白（Sp1），但没有典型的TATA或CAAT盒。该启动子在垂体源性GH4 C1细胞中表现出较强的活性，其-697 ~-596bp的区域负责forskolin的刺激和cAMP反应元件结合蛋白（CREB）的过表达。这些刺激显着抑制与溴隐亭孵育的剂量和时间依赖性的方式，和突变CREB（S133 A）完全废除溴隐亭的抑制事件。然而，EMSA研究表明，CREB并不结合到这个区域，大约60 kDa的蛋白质强烈结合，并且针对CREB，c-Fos和Sp1的抗体并没有超移位这个复合物。此外，用溴隐亭处理后，这种未知蛋白质的量明显减少。一系列突变分析表明，特异性序列5 '-cccacatcat-3'是与60-kDa蛋白结合和溴隐亭抑制所必需的。因此，溴隐亭对PrRPR基因的转录抑制需要CREB，但不依赖于CREB与该基因的直接结合，与60-kDa蛋白结合的序列-663-672，5 '-cccacatcat-3'似乎对该事件至关重要。
PRL-releasing peptide receptor (PrRPR) mRNA was expressed in pituitary adenomas but was not detected in patients treated with bromocriptine, a specific agonist of dopamine 2 (D2) receptor. Although medical treatment with bromocriptine is effective for patients with pituitary adenomas, little is known about the molecular mechanisms of gene regulation mediated by D2 receptors. The cloned human PrRPR gene spanned approximately 2.0 kb and contained two exons and one intron. Two functional polyadenylation signals located at 510 and 714 bp downstream from the stop codon. A primer extension analysis demonstrated two major transcriptional start sites at 139 and 140 bp upstream from the translational start site and an additional minor site at -161. The promoter region contained several putative binding sites for transcriptional factors including pituitary-specific transcription factor (Pit 1), activator protein 1 (AP-1), and specificity protein (Sp1), but no typical TATA or CAAT box. This promoter showed the strong activity in the pituitary-derived GH4C1 cells, and the region between -697 and -596 bp was responsible for the stimulation both by forskolin and overexpression of cAMP response element binding protein (CREB). These stimulations were significantly suppressed by incubation with bromocriptine in a dose- and time-dependent manner, and the mutant CREB (S133A) completely abolished the inhibitory events of bromocriptine. However, EMSA studies demonstrated that CREB did not bind to this region, to which an approximately 60-kDa protein was strongly bound, and that antibodies against CREB, c-Fos, and Sp1 did not supershift this complex. Furthermore, the amount of this unknown protein was apparently reduced by treatment with bromocriptine. A series of mutation analyses demonstrated that the specific sequence, 5'-cccacatcat-3', was required for both the binding to the 60-kDa protein and the repression by bromocriptine. Therefore, the transcriptional repression of the PrRPR gene by bromocriptine required CREB but was independent of direct binding of CREB to the gene and that the sequence -663 -- -672, 5'-cccacatcat-3', bound to the 60-kDa protein appeared to be critical for this event.
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克隆大鼠多巴胺-D2 受体与腺苷酸环化酶和催乳素分泌抑制的偶联。
DOI：
--
发表时间：
1990
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Albert,PR;Neve,KA;Bunzow,JR;Civelli,O
通讯作者：
Civelli,O
影响因子：
5.8
作者：
HERMAN, V;FAGIN, J;MELMED, S
通讯作者：
MELMED, S
刺激 3,5-单磷酸腺苷和 Ca2 信使系统共同逆转催乳素释放的多巴胺能抑制。
影响因子：
4.8
作者：
Delbeke,D;Dannies,PS
通讯作者：
Dannies,PS
多巴胺抑制大鼠垂体前叶中 32P 掺入磷脂酰肌醇。
影响因子：
4.8
作者：
Canonico,PL;Valdenegro,CA;Macleod,RM
通讯作者：
Macleod,RM
编码人前促甲状腺素释放激素的人基因组 DNA 和下丘脑 cDNA 的克隆和结构。
DOI：
10.1210/mend-4-4-551
发表时间：
1990
期刊：
Molecular endocrinology (Baltimore, Md.)
影响因子：
--
作者：
Yamada,M;Radovick,S;Wondisford,FE;Nakayama,Y;Weintraub,BD;Wilber,JF
通讯作者：
Wilber,JF