G proteins were originally discovered through efforts to understand the effects of hormones, such as glucagon and epinephrine, on glucose metabolism. On the other hand, many cellular metabolites, including glucose, serve as ligands for G protein-coupled receptors. Here we investigate the consequences of glucose-mediated receptor signaling, and in particular the role of a Gα subunit Gpa2 and a non-canonical Gβ subunit, known as Asc1 in yeast and RACK1 in animals. Asc1/RACK1 is of particular interest because it has multiple, seemingly unrelated, functions in the cell. The existence of such moonlighting operations has complicated the determination of phenotype from genotype. Through a comparative analysis of individual gene deletion mutants, and by integrating transcriptomics and metabolomics measurements, we have determined the relative contributions of the Gα and Gβ protein subunits to glucose-initiated processes in yeast. We determined that Gpa2 is primarily involved in regulating sugar metabolism while Asc1 is primarily involved in amino acid metabolism. Both proteins are involved in regulating purine metabolism. Of the two subunits, Gpa2 regulates a greater number of gene transcripts and was particularly important in determining the amplitude of response to glucose addition. We conclude that the two G protein subunits regulate distinct but complementary processes downstream of the glucose-sensing receptor, as well as processes that leadultimately to changes in cell growth and metabolism.

中文翻译：

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月光下的Gβ蛋白Asc1 / RACK1对葡萄糖介导的信号传导的多组学分析

G蛋白最初是通过努力了解诸如胰高血糖素和肾上腺素等激素对葡萄糖代谢的作用而发现的。另一方面，许多细胞代谢产物（包括葡萄糖）充当G蛋白偶联受体的配体。在这里，我们研究了葡萄糖介导的受体信号转导的后果，尤其是Gα亚基Gpa2和非经典Gβ亚基（在酵母中称为Asc1，在动物中称为RACK1）的作用。Asc1 / RACK1特别令人感兴趣，因为它在单元中具有多个看似无关的功能。这种月光照明操作的存在使根据基因型确定表型变得复杂。通过对单个基因缺失突变体的比较分析，以及整合转录组学和代谢组学测量，我们已经确定了Gα和Gβ蛋白亚基对酵母中葡萄糖启动过程的相对贡献。我们确定Gpa2主要参与调节糖代谢，而Asc1主要参与氨基酸代谢。两种蛋白质都参与调节嘌呤的代谢。在这两个亚基中，Gpa2调节着更多的基因转录本，在确定对葡萄糖添加的反应幅度方面尤其重要。我们得出的结论是，这两个G蛋白亚基调节葡萄糖传感受体下游的独特但互补的过程，以及最终导致细胞生长和代谢变化的过程。我们确定Gpa2主要参与调节糖代谢，而Asc1主要参与氨基酸代谢。两种蛋白质都参与调节嘌呤的代谢。在这两个亚基中，Gpa2调节着更多的基因转录本，在确定对葡萄糖添加的反应幅度方面尤其重要。我们得出的结论是，这两个G蛋白亚基调节葡萄糖传感受体下游的独特但互补的过程，以及最终导致细胞生长和代谢变化的过程。我们确定Gpa2主要参与调节糖代谢，而Asc1主要参与氨基酸代谢。两种蛋白质都参与调节嘌呤的代谢。在这两个亚基中，Gpa2调节着更多的基因转录本，在确定对葡萄糖添加的反应幅度方面尤其重要。我们得出的结论是，这两个G蛋白亚基调节葡萄糖传感受体下游的独特但互补的过程，以及最终导致细胞生长和代谢变化的过程。