G protein-coupled receptor-mediated ERK1/2 phosphorylation: towards a generic sensor of GPCR activation.
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: Galphas, Galphai and Galphaq. GPCR-mediated ERK phosphorylation was compared with different readouts such as GTPgammaS, 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.
Leroy
Didier
D
Department of Molecular Screening and Cellular Pharmacology, Serono Pharmaceutical Research Institute, CH-1228 Plan-les-Ouates, Geneva, Switzerland. leroy@serono.com
Missotten
Marc
M
Waltzinger
Caroline
C
Martin
Thierry
T
Scheer
Alexander
A
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D008024:Ligands; D010766:Phosphorylation; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction
D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D048049:Extracellular Signal-Regulated MAP Kinases; D019204:GTP-Binding Proteins