Functional selectivity profiling of the angiotensin II type 1 receptor using pathway-wide BRET signaling sensors
Yoon Namkung(McGill University Health Centre), Christian LeGouill(Institute for Research in Immunology and Cancer), Sahil Kumar(McGill University Health Centre), Yubo Cao(McGill University), Larissa B. Teixeira(Universidade de Ribeirão Preto), Viktoriya Lukasheva(Institute for Research in Immunology and Cancer), Jenna Giubilaro(McGill University), Sarah C. Simões(Universidade de Ribeirão Preto), Jean‐Michel Longpré(Université de Sherbrooke), Dominic Devost(McGill University), Terence E. Hébert(McGill University), Graciela Piñeyro(Centre Hospitalier Universitaire Sainte-Justine), Richard Leduc(Université de Sherbrooke), Cláudio M. Costa-Neto(Universidade de Ribeirão Preto), Michel Bouvier(Institute for Research in Immunology and Cancer), Stéphane A. Laporte(McGill University Health Centre)
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Abstract
and β-arrestin, there are also biases among G protein subtypes. We also demonstrated that biases observed at the receptor and G protein levels propagated to downstream signaling pathways and that these biases could occur through the engagement of different G proteins to activate a common effector. We also used these tools to determine how naturally occurring AT1R variants affected signaling bias. This suite of BRET biosensors provides a useful resource for fingerprinting biased ligands and mutant receptors and for dissecting functional selectivity at various levels of GPCR signaling.
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