ArticleThe Journal of biological chemistry2010
Human beta1-adrenergic receptor is subject to constitutive and regulated N-terminal cleavage.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 45 citations in OpenAlex.
- Altered O-glycosylation of βThe FEBS journal · 2025Article
- Protein glycosylation in cardiovascular health and disease.Nature reviews. Cardiology · 2024Review
- Substrate O-glycosylation actively regulates extracellular proteolysis.Protein science : a publication of the Protein Society · 2024Article
- Cardiomyocyte-specific overexpression of GPR22 ameliorates cardiac injury in mice with acute myocardial infarction.BMC cardiovascular disorders · 2024Article
- Dissecting Beta-Adrenergic Receptors: The Sum of Many Parts.JACC. Basic to translational science · 2023Article
- NTSR1 glycosylation and MMP dependent cleavage generate three distinct forms of the protein.Scientific reports · 2023Article
- Emerging Roles for the Orphan GPCRs, GPR37 and GPR37 L1, in Stroke Pathophysiology.International journal of molecular sciences · 2022Review
- Proteolytic Cleavage of the Extracellular Domain Affects Signaling of Parathyroid Hormone 1 Receptor.Frontiers in endocrinology · 2022Article
- GPR37 is processed in the N-terminal ectodomain by ADAM10 and furin.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- βJournal of molecular and cellular cardiology · 2021Article
- The N-terminus of GPR37L1 is proteolytically processed by matrix metalloproteases.Scientific reports · 2020Article
- N-glycosylation of αScientific reports · 2020Article
- G Protein-Coupled Receptors in the Sweet Spot: Glycosylation and other Post-translational Modifications.ACS pharmacology & translational science · 2020Review
- βScientific reports · 2017Article
- Site-specificThe Journal of biological chemistry · 2017Article
- Endogenous N-terminal Domain Cleavage Modulates α1D-Adrenergic Receptor Pharmacodynamics.The Journal of biological chemistry · 2016Article
- Global Mapping of O-Glycosylation of Varicella Zoster Virus, Human Cytomegalovirus, and Epstein-Barr Virus.The Journal of biological chemistry · 2016Article
- A systematic study of modulation of ADAM-mediated ectodomain shedding by site-specific O-glycosylation.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- A sensor of protein O-glycosylation based on sequential processing in the Golgi apparatus.Traffic (Copenhagen, Denmark) · 2013Article
- The relationship between the MMP system, adrenoceptors and phosphoprotein phosphatases.British journal of pharmacology · 2012Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The beta(1)-adrenergic receptor (beta(1)AR) is the predominant betaAR in the heart, mediating the catecholamine-stimulated increase in cardiac rate and force of contraction. Regulation of this important G protein-coupled receptor is nevertheless poorly understood. We describe here the biosynthetic profile of the human beta(1)AR and reveal novel features relevant to its regulation using an inducible heterologous expression system in HEK293(i) cells. Metabolic pulse-chase labeling and cell surface biotinylation assays showed that the synthesized receptors are efficiently and rapidly transported to the cell surface. The N terminus of the mature receptor is extensively modified by sialylated mucin-type O-glycosylation in addition to one N-glycan attached to Asn(15). Furthermore, the N terminus was found to be subject to limited proteolysis, resulting in two membrane-bound C-terminal fragments. N-terminal sequencing of the fragments identified two cleavage sites between Arg(31) and Leu(32) and Pro(52) and Leu(53), which were confirmed by cleavage site and truncation mutants. Metalloproteinase inhibitors were able to inhibit the cleavage, suggesting that it is mediated by a matrix metalloproteinase or a disintegrin and metalloproteinase (ADAM) family member. Most importantly, the N-terminal cleavage was found to occur not only in vitro but also in vivo. Receptor activation mediated by the betaAR agonist isoproterenol enhanced the cleavage in a concentration- and time-dependent manner, and it was also enhanced by direct stimulation of protein kinase C and adenylyl cyclase. Mutation of the Arg(31)-Leu(32) cleavage site stabilized the mature receptor. We hypothesize that the N-terminal cleavage represents a novel regulatory mechanism of cell surface beta(1)ARs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.