Signal profiling of the β₁AR reveals coupling to novel signalling pathways and distinct phenotypic responses mediated by β₁AR and β₂AR.

ABSTRACT: A comprehensive understanding of signalling downstream of GPCRs requires a broad approach to capture novel signalling modalities in addition to established pathways. Here, using an array of sixteen validated BRET-based biosensors, we analyzed the ability of seven different β-adrenergic ligands to engage five distinct signalling pathways downstream of the β₁-adrenergic receptor (β₁AR). In addition to generating signalling signatures and capturing functional selectivity for the different ligands toward these pathways, we also revealed coupling to signalling pathways that have not previously been ascribed to the βAR. These include coupling to G_z and G₁₂ pathways. The signalling cascade linking the β₁AR to calcium mobilization was also cha

SUBMITTER: Lukasheva V 

PROVIDER: S-EPMC7260363 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature