Extended Human G-Protein Coupled Receptor Network: Cell-Type-Specific Analysis of G-Protein Coupled Receptor Signaling Pathways
Extended Human G-Protein Coupled Receptor Network: Cell-Type-Specific Analysis of G-Protein Coupled Receptor Signaling Pathways
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DOI：
10.1021/acs.jproteome.9b00754
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发表时间：
2020-01-01
影响因子：
4.4
通讯作者：
Iconomidou, Vassiliki A.
中科院分区：
文献类型：
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作者：
Apostolakou, Avgi E.;Baltoumas, Fotis A.;Iconomidou, Vassiliki A.
G蛋白偶联受体(GPCRs)在人体内介导着重要的生理功能，与多种疾病有关，因此是主要的药物靶点。GPCRs通过多种途径发出信号，主要通过G蛋白和β-阻滞素来调节负责细胞反应的效应器。转导分子的数量有限导致不同的GPCRs在同一途径上发挥控制作用，而细胞中信号蛋白的可获得性决定了GPCRs激活的结果。本研究的目的是构建扩展的人类GPCRnet网络(HGPCRnet)，并检测细胞类型特异性对GPCR信号通路的影响。为了实现这一点，GPCRs、G蛋白偶联受体激酶(GRKs)、Gα亚基、β-阻滞剂和效应器之间的蛋白质相互作用数据与细胞类型的蛋白质表达数据相结合。这导致了hGPCRnet，一个非常大的相互连接的网络，以及类似的细胞类型特定的网络，在其中形成了不同的GPCR信号通路。最后，创建了一个用户友好的网络应用程序hGPCRnet(http://bioinformatics.biol.uoa.gr/hGPCRnet)，)，以允许可视化和探索这些网络和GPCRi信号通路。这项工作和由此产生的应用，可用于进一步研究gpr的功能和药理学。
G-protein coupled receptors (GPCRs) mediate crucial physiological functions in humans, have been implicated in an array of diseases, and are therefore prime drug targets. GPCRs signal via a multitude of pathways, mainly through G-proteins and beta-arrestins, to regulate effectors responsible for cellular responses. The limited number of transducers results in different GPCRs exerting control on the same pathway, while the availability of signaling proteins in a cell defines the result of GPCR activation. The aim of this study was to construct the extended human GPCR network (hGPCRnet) and examine the effect that cell-type specificity has on GPCR signaling pathways. To achieve this, protein-protein interaction data between GPCRs, G-protein coupled receptor kinases (GRKs), G alpha subunits, beta-arrestins, and effectors were combined with protein expression data in cell types. This resulted in the hGPCRnet, a very large interconnected network, and similar cell-type-specific networks in which, distinct GPCR signaling pathways were formed. Finally, a user friendly web application, hGPCRnet (http://bioinformatics.biol.uoa.gr/hGPCRnet), was created to allow for the visualization and exploration of these networks and of GPCR signaling pathways. This work, and the resulting application, can be useful in further studies of GPCR function and pharmacology.