Phosphoproteomic Analysis of Dopamine D2 Receptor Signaling Reveals Interplay of G Protein- and β-Arrestin-Mediated Effects.

ABSTRACT: Leveraging biased signaling of G protein-coupled receptors has been proposed as a promising strategy for the development of drugs with higher specificity. However, the consequences of selectively targeting G protein- or β-arrestin-mediated signaling on cellular functions are not comprehensively understood. In this study, we utilized phosphoproteomics to gain a systematic overview of signaling induced by the four biased and balanced dopamine D2 receptor (D₂R) ligands MS308, BM138, quinpirole, and sulpiride in an in vitro D₂R transfection model. Quantification of 14,160 phosphosites revealed a low impact of the partial G protein agonist MS308 on cellular protein phosphorylation, as well as surprising similarities between the balanced agonist quinpirole and the inverse a

SUBMITTER: Wenk D 

PROVIDER: S-EPMC9831068 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature