Noncanonical scaffolding of G_αi and β-arrestin by G protein-coupled receptors.

ABSTRACT: Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) are common drug targets and canonically couple to specific G_α protein subtypes and β-arrestin adaptor proteins. G protein-mediated signaling and β-arrestin-mediated signaling have been considered separable. We show here that GPCRs promote a direct interaction between G_αi protein subtype family members and β-arrestins regardless of their canonical G_α protein subtype coupling. G_αi:β-arrestin complexes bound extracellular signal-regulated kinase (ERK), and their disruption impaired both ERK activation and cell migration, which is consistent with β-arrestins requiring a functional interaction with G_αi for certain signaling events. These results introduc

SUBMITTER: Smith JS 

PROVIDER: S-EPMC8005335 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature