Role of third intracellular loop of the melanocortin 4 receptor in the regulation of constitutive activity
Role of third intracellular loop of the melanocortin 4 receptor in the regulation of constitutive activity
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DOI：
10.1016/j.bbrc.2007.10.170
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发表时间：
2008-01-18
影响因子：
3.1
通讯作者：
Baik, Ja-Hyun
中科院分区：
文献类型：
--
作者：
Kim, Do-Hun;Shin, Seung Woo;Baik, Ja-Hyun
黑皮质素4受体（MC4R）已被报道显示组成性活动，这可能是相关的维持正常的能量平衡。在临床报道的人类肥胖患者MC4R突变体中，我们研究了以MC4R第三胞内（D）环突变为特征的7种突变体的功能特征。通过CRE（cAMP反应元件）介导的荧光素酶报告基因测定，我们发现，这些突变体中的大多数显示显着降低的基础活性与报告基因活性降低，而P230 L突变体表现出显着增加的基础活性。当显性负G（s）突变体共表达时，包括P230L突变体在内的大多数突变体显示出降低的基础活性。这些结果表明，MC4R的D环不仅是必不可少的功能活动，但也为调节和维持最佳的组成活动的MC4R与G蛋白偶联，在控制能量稳态。(c)2007年爱思唯尔公司All rights reserved.
The melanocortin 4 receptor (MC4R) has been reported to display constitutive activity, which is probably relevant to the maintenance of a normal energy balance. Among the clinically reported mutants of MC4R in human obesity patients, we investigated the functional characteristics of seven mutants characterized by mutations in the third intracellular (D) loop of MC4R. Via a CRE (cAMP responsive element)-mediated luciferase reporter gene assay, we show that most of these mutants displayed significantly reduced basal activity with reduced reporter gene activity, whereas the P230L mutant manifested significantly increased basal activity. When the dominant negative G(s) mutant was co-expressed, the majority of the mutants, including the P230L mutant, showed reduced basal activity. These results suggest that the D loop of MC4R is essential not only for the functional activity but also for the regulation and maintenance of an optimal constitutive activity of MC4R in association with G protein coupling, in the control of energy homeostasis. (c) 2007 Elsevier Inc. All rights reserved.