Back to Search
Start Over
Noncanonical scaffolding of G αi and β-arrestin by G protein-coupled receptors.
- Source :
-
Science (New York, N.Y.) [Science] 2021 Mar 12; Vol. 371 (6534). Date of Electronic Publication: 2021 Jan 21. - Publication Year :
- 2021
-
Abstract
- Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) are common drug targets and canonically couple to specific G <subscript>α</subscript> 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 <subscript>αi</subscript> protein subtype family members and β-arrestins regardless of their canonical G <subscript>α</subscript> protein subtype coupling. G <subscript>αi</subscript> :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 <subscript>αi</subscript> for certain signaling events. These results introduce a GPCR signaling mechanism distinct from canonical G protein activation in which GPCRs cause the formation of G <subscript>αi</subscript> :β-arrestin signaling complexes.<br /> (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Details
- Language :
- English
- ISSN :
- 1095-9203
- Volume :
- 371
- Issue :
- 6534
- Database :
- MEDLINE
- Journal :
- Science (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 33479120
- Full Text :
- https://doi.org/10.1126/science.aay1833