β₁-adrenergic receptor O-glycosylation regulates N-terminal cleavage and signaling responses in cardiomyocytes.

ABSTRACT: β₁-adrenergic receptors (β₁ARs) mediate catecholamine actions in cardiomyocytes by coupling to both Gs/cAMP-dependent and Gs-independent/growth-regulatory pathways. Structural studies of the β₁AR define ligand-binding sites in the transmembrane helices and effector docking sites at the intracellular surface of the β₁AR, but the extracellular N-terminus, which is a target for post-translational modifications, typically is ignored. This study identifies β₁AR N-terminal O-glycosylation at Ser³⁷/Ser⁴¹ as a mechanism that prevents β₁AR N-terminal cleavage. We used an adenoviral overexpression strategy to show that both full-length/glycosylated β₁ARs and N-terminally truncated glycosylation-defecti

SUBMITTER: Park M 

PROVIDER: S-EPMC5554155 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature