Ligands can differentially and temporally modulate GPCR interaction with 14-3-3 isoforms

Q2 Agricultural and Biological Sciences Current Research in Pharmacology and Drug Discovery Pub Date : 2022-01-01 DOI:10.1016/j.crphar.2022.100123

Haifeng Eishingdrelo , Xiaofa Qin , Luwa Yuan , Sathapana Kongsamut , Lei Yu

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引用次数: 1

Abstract

GPCR signaling and function depend on their associated proteins and subcellular locations. Besides G-proteins and β-arrestins, 14-3-3 proteins participate in GPCR trafficking and signaling, and they connect a large number of diverse proteins to form signaling networks. Multiple 14-3-3 isoforms exist, and a GPCR can differentially interact with different 14-3-3 isoforms in response to agonist treatment. We found that some agonist-induced GPCR/14-3-3 signal intensities can rapidly decrease. We confirmed that this phenomenon of rapidly decreasing agonist-induced GPCR/14-3-3 signal intensity could also be paralleled with GPCR/β-arrestin-2 signals, indicating diminished levels of GPCR/signal adaptor complexes during endocytosis. The temporal signals could implicate either GPCR/14-3-3 complex dissociation or the complex undergoing a degradation process. Furthermore, we found that certain GPCR ligands can regulate GPCR/14-3-3 signals temporally, suggesting a new approach for GPCR drug development by modulating GPCR/14-3-3 signals temporally.

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配体可以对GPCR与14-3-3异构体的相互作用进行差异性和临时性调节

GPCR信号和功能取决于其相关蛋白和亚细胞位置。除了g蛋白和β-阻滞蛋白外，14-3-3蛋白还参与GPCR的转运和信号传递，它们将大量不同的蛋白连接起来形成信号网络。存在多种14-3-3异构体，GPCR在激动剂处理下可与不同的14-3-3异构体发生不同的相互作用。我们发现一些激动剂诱导的GPCR/14-3-3信号强度可以迅速降低。我们证实，这种激动剂诱导的GPCR/14-3-3信号强度迅速降低的现象也可能与GPCR/β-arrestin-2信号平行，表明在吞吞过程中GPCR/信号接头复合物的水平降低。时间信号可能暗示GPCR/14-3-3复合物解离或复合物正在进行降解过程。此外，我们发现某些GPCR配体可以暂时调节GPCR/14-3-3信号，提示通过暂时调节GPCR/14-3-3信号来开发GPCR药物的新途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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