Isoprenaline shows unique kinase dependencies in stimulating β₁AR-β-arrestin2 interaction compared to endogenous catecholamines.

ABSTRACT: The β1-adrenergic receptor (β₁AR) is an essential G protein-coupled receptor in the heart. Its dysregulation represents a hallmark of cardiac diseases. Studies have identified a unique mode of β-arrestin interaction, where β₁AR briefly engages with β-arrestins before catalytically accumulating them at the plasma membrane (PM) independently of the receptor. Although receptor phosphorylation crucially impacts β-arrestins, the contributions of specific kinases vital in β₁AR regulation remain unclear. Here, we employed G protein-coupled receptor kinase (GRK) GRK2/3/5/6 knockout cells and the protein kinase A inhibitor H89 in bioluminescence resonance energy transfer-based assays to systematically assess GRKs and protein kinase A in direct β-arrestin2 recruitmen

SUBMITTER: Matthees ESF 

PROVIDER: S-EPMC12264555 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature