Approaches to Assess Functional Selectivity in GPCRs: Evaluating G Protein Signaling in an Endogenous Environment.
Approaches to Assess Functional Selectivity in GPCRs: Evaluating G Protein Signaling in an Endogenous Environment.
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DOI：
10.1007/978-1-4939-2914-6_12
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发表时间：
2015-01-01
期刊：
影响因子：
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通讯作者：
Ho, Jo-Hao
中科院分区：
文献类型：
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作者：
Bohn, Laura M;Zhou, Lei;Ho, Jo-Hao
配体定向信号传导、偏向激动和功能选择性是描述配体驱动信号传导朝向一个GPCR途径而非另一个途径的倾向的术语。迄今为止，大多数早期的例子都证明了GPCR信号与G蛋白偶联和β抑制蛋白2募集之间的差异。随着基于细胞的筛选标准的偏向性激动剂开始变得可用，需要确定G蛋白信号传导偏向性是否将维持在内源性环境中，其中受体起作用以控制相关的生物反应。这份报告介绍了我们的方法，并提供了提示评估G蛋白信号在内源性组织。这里主要讨论脑组织;可以应用于任何组织的优化点被突出显示。
Ligand-directed signaling, biased agonism, and functional selectivity are terms that describe the propensity of a ligand to drive signaling toward one GPCR pathway over another. Most of the early examples demonstrated to date examine the divergence between GPCR signaling to G protein coupling and betaarrestin2 recruitment. As biased agonists begin to become available based on cell-based screening criteria, a need arises to determine if G protein signaling biases will be maintained in the endogenous setting, wherein receptors are functioning to control relevant biological responses. This report presents our method and offers tips for evaluating G protein signaling in endogenous tissues. Predominately, brain tissues are discussed here; optimization points that can be applied to any tissues are highlighted.