Non-canonical β-adrenergic activation of ERK at endosomes.

ABSTRACT: G-protein-coupled receptors (GPCRs), the largest family of signalling receptors, as well as important drug targets, are known to activate extracellular-signal-regulated kinase (ERK)-a master regulator of cell proliferation and survival¹. However, the precise mechanisms that underlie GPCR-mediated ERK activation are not clearly understood^2-4. Here we investigated how spatially organized β₂-adrenergic receptor (β₂AR) signalling controls ERK. Using subcellularly targeted ERK activity biosensors⁵, we show that β₂AR signalling induces ERK activity at endosomes, but not at the plasma membrane. This pool of ERK activity depends on active, endosome-localized Gα_s and requires ligand-stimulated β₂AR endocytosis.

SUBMITTER: Kwon Y 

PROVIDER: S-EPMC10031817 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature