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首页> 外文期刊>Cellular Signalling >Interaction of G beta 3s, a splice variant of the G-protein G beta 3, with G gamma- and G alpha-proteins
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Interaction of G beta 3s, a splice variant of the G-protein G beta 3, with G gamma- and G alpha-proteins

机译：G beta 3s（G蛋白G beta 3的剪接变体）与Gamma和G alpha蛋白的相互作用

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摘要

The T-allele of a polymorphism (C825T) in the gene of the G-protein beta-subunit is associated with a complex phenotype (hypertension, obesity, altered drug responses) and the occurrence of a splice variant termed Gbeta3s which lacks one of the seven WD-domains that compose Gbeta-proteins. Here, we analysed Gbetagamma dimer formation and Galpha activation by Gbeta3s, key functional characteristics of Gbeta-proteins. Cleavage protection assays frequently used to analyse Gbeta1gamma and Gbeta2gamma dimer formation failed for Gbeta3 and Gbeta3s, while in coprecipitation assays, dimerization of Gbeta3 and Gbeta3s with Ggamma5, Ggamma8(c) and Ggamma12 could be demonstrated. Upon expression of Gbeta3s in COS-7 and Sf9 insect cells, binding of GTPgammaS to Galpha-proteins induced by mastoparan-7 and the M-2 muscarinic acetylcholine receptor was facilitated in comparison with cells overexpressing wildtype Gbeta3, as indicated by twofold reduced agonist EC50 values. Together, these results indicate that Gbeta3s is a biologically active Gbeta-protein that may mediate the enhanced signal transduction observed in cells with the 825T-allele. (C) 2002 Elsevier Science Inc. All rights reserved. [References: 58]
机译：G蛋白β亚基基因的多态性（C825T）的T等位基因与复杂的表型（高血压，肥胖，药物反应改变）和称为Gbeta3s的剪接变体的出现有关，该变体缺少一种七个组成Gbeta蛋白的WD结构域。在这里，我们分析了Gbetagamma二聚体的形成和Gbeta3s（Gbeta蛋白的关键功能特征）对Galpha的激活。经常用于分析Gbeta1gamma和Gbeta2gamma二聚体形成的裂解保护测定法对Gbeta3和Gbeta3s失败，而在共沉淀测定法中，可以证明Gbeta3和Gbeta3与Ggamma5，Ggamma8（c）和Ggamma12的二聚化。与过量表达野生型Gbeta3的细胞相比，激动剂EC50降低了两倍，在COS-7和Sf9昆虫细胞中表达Gbeta3s后，与过表达野生型Gbeta3的细胞相比，促进了GTPgammaS与由mastoparan-7和M-2毒蕈碱型乙酰胆碱受体诱导的Galpha蛋白结合。价值观。总之，这些结果表明Gbeta3s是一种生物活性Gbeta蛋白，可以介导在825T等位基因细胞中观察到的增强的信号转导。 （C）2002 Elsevier Science Inc.保留所有权利。 [参考：58]

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