GPCR screening via ERK 1/2: a novel platform for screening G protein-coupled receptors |
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Authors: | Osmond Ronald I W Sheehan Antony Borowicz Romana Barnett Emma Harvey Georgina Turner Cheryl Brown Andrea Crouch Michael F Dyer Anthony R |
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Institution: | TGR BioSciences Pty Ltd, 31 Dalgleish Street, Thebarton, SA 5031, Australia. |
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Abstract: | 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 inositol 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. |
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