Noncanonical scaffolding of Gαi and ß-arrestin by G protein-coupled receptors.
Science
; 371(6534)2021 03 12.
Article
em En
| MEDLINE
| ID: mdl-33479120
ABSTRACT
Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) are common drug targets and canonically couple to specific Gα protein subtypes and ß-arrestin adaptor proteins. G protein-mediated signaling and ß-arrestin-mediated signaling have been considered separable. We show here that GPCRs promote a direct interaction between Gαi protein subtype family members and ß-arrestins regardless of their canonical Gα protein subtype coupling. Gαiß-arrestin complexes bound extracellular signal-regulated kinase (ERK), and their disruption impaired both ERK activation and cell migration, which is consistent with ß-arrestins requiring a functional interaction with Gαi for certain signaling events. These results introduce a GPCR signaling mechanism distinct from canonical G protein activation in which GPCRs cause the formation of Gαiß-arrestin signaling complexes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP
/
Receptores Acoplados a Proteínas G
/
Beta-Arrestinas
Limite:
Humans
Idioma:
En
Revista:
Science
Ano de publicação:
2021
Tipo de documento:
Article