Gαs is dispensable for β-arrestin coupling but dictates GRK selectivity and is predominant for gene expression regulation by β2-adrenergic receptor.
Humans
beta-Arrestin 1
/ genetics
beta-Arrestin 2
/ genetics
beta-Arrestins
/ genetics
Cyclic AMP-Dependent Protein Kinases
/ metabolism
Gene Expression Regulation
/ genetics
GTP-Binding Proteins
/ metabolism
Mitogen-Activated Protein Kinases
/ metabolism
Phosphorylation
Receptors, Adrenergic, beta-2
/ chemistry
HEK293 Cells
GTP-Binding Protein alpha Subunits
/ genetics
Protein Structure, Tertiary
Protein Isoforms
Enzyme Activation
/ genetics
G protein
G protein–coupled receptor
gene expression
signaling
β-arrestin
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
15
02
2023
revised:
03
09
2023
accepted:
14
09
2023
medline:
27
11
2023
pubmed:
30
9
2023
entrez:
29
9
2023
Statut:
ppublish
Résumé
β-arrestins play a key role in G protein-coupled receptor (GPCR) internalization, trafficking, and signaling. Whether β-arrestins act independently of G protein-mediated signaling has not been fully elucidated. Studies using genome-editing approaches revealed that whereas G proteins are essential for mitogen-activated protein kinase activation by GPCRs., β-arrestins play a more prominent role in signal compartmentalization. However, in the absence of G proteins, GPCRs may not activate β-arrestins, thereby limiting the ability to distinguish G protein from β-arrestin-mediated signaling events. We used β2-adrenergic receptor (β2AR) and its β2AR-C tail mutant expressed in human embryonic kidney 293 cells wildtype or CRISPR-Cas9 gene edited for Gα
Identifiants
pubmed: 37774973
pii: S0021-9258(23)02321-9
doi: 10.1016/j.jbc.2023.105293
pmc: PMC10641165
pii:
doi:
Substances chimiques
beta-Arrestin 1
0
beta-Arrestin 2
0
beta-Arrestins
0
Cyclic AMP-Dependent Protein Kinases
EC 2.7.11.11
GTP-Binding Proteins
EC 3.6.1.-
Mitogen-Activated Protein Kinases
EC 2.7.11.24
Receptors, Adrenergic, beta-2
0
GTP-Binding Protein alpha Subunits
0
Protein Isoforms
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
105293Subventions
Organisme : NCI NIH HHS
ID : U54 CA209891
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA273974
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA217885
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA274502
Pays : United States
Organisme : NLM NIH HHS
ID : T15 LM011271
Pays : United States
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest J. S. G. is consultant for Domain Therapeutics, Pangea Therapeutics, and io9, and founder of Kadima Pharmaceuticals, outside the submitted work. M. B. is the president of Domain Therapeutics Scientific Advisory Board. The authors declare that they have no conflicts of interest with the contents of this article.