G Protein-Coupled Receptor-Mediated ERK1/2 Phosphorylation: Towards a Generic Sensor of GPCR Activation |
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Authors: | DIDIER LEROY MARC MISSOTTEN CAROLINE WALTZINGER THIERRY MARTIN ALEXANDER SCHEER |
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Institution: | Department of Molecular Screening and Cellular Pharmacology, Serono Pharmaceutical Research Institute, CH-1228 Plan-les-Ouates, Geneva, Switzerland |
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Abstract: | The development of new analytical methods, aimed at profiling G protein-coupled receptor (GPCR) ligands, regardless of the G protein-coupling pattern of their respective receptor, remains a key goal in drug discovery. Considerable evidence has recently revived the central role that could be played by extracellular-signal-regulated kinase (ERK), the cornerstone protein kinase of the first tyrosine kinase receptor-mediated pathway identified, in response to the activation of various types of GPCRs. Here we reveal a conceptual study in which the potential of ERK phosphorylation is evaluated as a generic readout in response to three different receptors activating three main classes of G proteins: Gαs, Gαi and Gα q. GPCR-mediated ERK phosphorylation was compared with different readouts such as GTPγ S, CAMP, or Ca2 +. We propose the measurement of GPCR-activated ERK phosphorylation as an alternative assay to better understand the molecular pharmacology of ligands of promiscuous GPCRs. |
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Keywords: | ERK1/2 phosphorylation GPCRs Drug discovery |
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