Mechanoactivation of the angiotensin II type 1 receptor induces β-arrestin-biased signaling through Gα_i coupling.

ABSTRACT: Ligand activation of the angiotensin II type 1 receptor (AT1R), a member of the G protein-coupled receptor (GPCR) family, stimulates intracellular signaling to mediate a variety of physiological responses. The AT1R is also known to be a mechanical sensor. When activated by mechanical stretch, the AT1R can signal via the multifunctional adaptor protein β-arrestin, rather than through classical heterotrimeric G protein pathways. To date, the AT1R conformation induced by membrane stretch in the absence of ligand was thought to be the same as that induced by β-arrestin-biased agonists, which selectively engage β-arrestin thereby preventing G protein coupling. Here, we show that in contrast to the β-arrestin-biased agonists TRV120023 and TRV120026, membrane stretch uniquely promotes the couplin

SUBMITTER: Wang J 

PROVIDER: S-EPMC5826900 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature