GPCR screening via ERK 1/2: A novel platform for screening G protein-coupled receptors
GPCR screening via ERK 1/2: A novel platform for screening G protein-coupled receptors
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DOI：
10.1177/1087057105277968
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发表时间：
2005-10-01
影响因子：
--
通讯作者：
Dyer, AR
中科院分区：
文献类型：
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作者：
Osmond, RIW;Sheehan, A;Dyer, AR
G蛋白偶联受体（GPCR）的新型激动剂和拮抗剂的发现在很大程度上依赖于基于细胞的测定，因为测定受体接合的功能后果通常是期望的。目前，有几个关键参数测量，以实现这一目标，包括细胞内Ca 2+的动员和形成环腺苷酸或三磷酸肌醇。然而，没有一个单一的测定平台适用于所有情况，并且所有测定都有局限性。作者开发了一种新的高通量均相检测平台，用于GPCR发现，作为当前检测的替代方法，该方法采用关键信号分子p42/44 MAP激酶（ERK 1/2）的磷酸化检测。作者表明，ERK 1/2在Gq偶联的GPCR刺激的细胞中持续活化，并为筛选GPCR药物候选物提供了一个新的高通量平台。ERK 1/2在Gq偶联GPCR系统中的活化产生了通过其他GPCR活化测量技术获得的受体激动剂和拮抗剂数据的可比药理学数据。
Discovery of novel agonists and antagonists for G protein-coupled receptors (GPCRs) relies heavily on cell-based assays because determination of functional consequences of receptor engagement is often desirable. Currently, there are several key parameters measured to achieve this, including mobilization of intracellular Ca2+ and formation of cyclic adenosine monophosphate or mositol triphosphate. However, no single assay platform is suitable for all situations, and all of the assays have limitations. The authors have developed a new high-throughput homogeneous assay platform for GPCR discovery as an alternative to current assays, which employs detection of phosphorylation of the key signaling molecule p42/44 MAP kinase (ERK 1/2). The authors show that ERK 1/2 is consistently activated in cells stimulated by Gq-coupled GPCRs and provides a new high-throughput platform for screening GPCR drug, candidates. The activation of ERK 1/2 in Gq-coupled GPCR systems generates comparable pharmacological data for receptor agonist and antagonist data obtained by other GPCR activation measurement techniques.