Multihormonal Regulation of Phosphoenolpyruvate Carboxykinase Gene Transcription
Multihormonal Regulation of Phosphoenolpyruvate Carboxykinase Gene Transcription
复制标题
磷酸烯醇丙酮酸羧激酶基因转录的多激素调节
DOI：
10.1111/j.1749-6632.1986.tb15530.x
复制
发表时间：
1986
影响因子：
5.2
通讯作者：
David T. W. Chu
中科院分区：
文献类型：
--
作者：
D. Granner;K. Sasaki;David T. W. Chu
我们实验室最重要的目标是了解几种激素（每一种可能都有独特的作用机制）如何提供综合的生物反应。我们集中研究了磷酸烯醇丙酮酸羧激酶（PEPCK） （EC 4.1.1.32）在培养的H4IIE细胞（Reuber H35大鼠肝癌细胞的克隆）中的调控作用。PEPCK催化草酸酯转化为磷酸烯醇丙酮酸，是一种限速糖异生酶。介导胰高血糖素作用的环AMP和糖皮质激素可提高该蛋白的合成速度，并促进糖异生。*2胰岛素降低PEPCK的合成速率，相应减少葡聚糖的生成。通过将PEPCK合成的测量与定量PEPCK (mRNApepcK) mRNA编码的活性和数量的测定相结合，我们能够排除以下可能性作为激素控制的手段：mRNApepcK翻译效率的改变，mRNApepcK从细胞核中输出速率的改变，以及mRNApepcK在细胞核或细胞质中的降解速率的变化。我们对这些研究的解释是CAMP、糖皮质激素和胰岛素影响mRNAPEPCK的产生。本文研究的目的是确定这些分子是否在PEPCK基因转录水平上调控PEPCK合成，然后探索它们是如何协同作用的。类固醇激素被认为通过影响特定基因的转录速率来调节代谢过程。这一作用的第一步涉及到配体与细胞内受体的结合。激素受体复合物以特定位点的方式与DNA结合，从而调节特定基因的转录。
The most important goal of our laboratory is to understand how several hormones, each of which presumably has a unique mechanism of action, provide an integrated biological response. We have concentrated our efforts on the regulation of the enzyme phosphoenolpyruvate carboxykinase (PEPCK) (EC 4.1.1.32) in cultured H4IIE cells, a clone of Reuber H35 rat hepatoma cells. PEPCK catalyzes the conversion of oxalacetate to phosphoenolpyruvate and is a rate-limiting gluconeogenic enzyme. Cyclic AMP, which mediates the action of glucagon, and glucocorticoids increase the rate of synthesis of this protein and enhance gluconeogenesis.'*2 Insulin decreases the rate of synthesis of PEPCK and correspondingly decreases glucone~genesis.'~~ By coupling measurements of PEPCK synthesis with assays capable of quantitating the activity and the amount of mRNA coding for PEPCK (mRNApepcK), we were able to exclude the following possibilities as means of hormonal control: alterations of mRNAPEPCK translational efficiency, alterations in the rate of mRNAPEPCK egress from the nucleus, and changes in the rate of degradation of mRNAPEPCK in the nucleus or cytoplasm.2-M Our interpretation of these studies was that CAMP, glucocorticoids, and insulin affect mRNAPEPCK production. The purpose of the studies described in this paper was to determine whether each of these molecules regulated PEPCK synthesis at the level of PEPCK gene transcription and then to explore how they acted in concert. Steroid hormones are thought to regulate metabolic processes by affecting the rate of transcription of specific genes. The first step in this action involves the binding of the ligand to intracellular receptors. The hormone-receptor complex binds in a sitespecific manner to DNA, and thereby regulates the transcription of specific genes.
登录
查看更多内容
大鼠肝胞质磷酸烯醇丙酮酸羧激酶 (GTP)。
DOI：
--
发表时间：
1985
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Beale,EG;Chrapkiewicz,NB;Scoble,HA;Metz,RJ;Quick,DP;Noble,RL;Donelson,JE;Biemann,K;Granner,DK
通讯作者：
Granner,DK
N6,O2-二丁酰循环 AMP 和葡萄糖调节编码肝磷酸烯醇丙酮酸羧激酶 (GTP) 的信使 RNA 的量。
DOI：
--
发表时间：
1982
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Beale,EG;Hartley,JL;Granner,DK
通讯作者：
Granner,DK
磷酸烯醇丙酮酸羧激酶基因转录的多激素调节。
DOI：
--
发表时间：
1984
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Sasaki,K;Cripe,TP;Koch,SR;Andreone,TL;Petersen,DD;Beale,EG;Granner,DK
通讯作者：
Granner,DK
胰岛素刺激 32Pi 掺入培养的支持细胞中的核糖核酸。
影响因子：
4.8
作者：
Griswold,MD;Merryweather,J
通讯作者：
Merryweather,J
基因表达的胰岛素调节。
DOI：
10.1002/dmr.5610010108
发表时间：
1985
期刊：
Diabetes/metabolism reviews
影响因子：
--
作者：
Granner,DK;Andreone,TL
通讯作者：
Andreone,TL