ArticlePhysiological genomics2013
S49G and R389G polymorphisms of the β₁-adrenergic receptor influence signaling via the cAMP-PKA and ERK pathways.
Article in Physiological genomics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 26 citations in OpenAlex.
- Pharmacogenomics-guided therapy for essential hypertension: a multi-center randomized controlled open-label trial.Frontiers in cardiovascular medicine · 2026Article
- βmedRxiv : the preprint server for health sciences · 2025Article
- Combining genetic proxies of drug targets and time-to-event analyses from longitudinal observational data to identify target patient populations.BMC cardiovascular disorders · 2025 · on this mapObservational
- Altered O-glycosylation of βThe FEBS journal · 2025Article
- Deciphering the Role of Calcium Signaling Pathway-Associated Single Nucleotide Variants in Susceptibility to Hypertension.Journal of clinical laboratory analysis · 2025Article
- Receptor Pharmacogenomics: Deciphering Genetic Influence on Drug Response.International journal of molecular sciences · 2024Review
- Signaling pathways in vascular function and hypertension: molecular mechanisms and therapeutic interventions.Signal transduction and targeted therapy · 2023Review
- Vasovagal Syncope Is Associated with Variants in Genes Involved in Neurohumoral Signaling Pathways.Genes · 2022Article
- Play the plug: How bacteria modify recognition by host receptors?Frontiers in microbiology · 2022Article
- Beta-adrenergic receptors gene polymorphisms are associated with cardiac contractility and blood pressure variability.Physiological research · 2021Article
- New Structural Perspectives in G Protein-Coupled Receptor-Mediated Src Family Kinase Activation.International journal of molecular sciences · 2021Review
- Carvedilol, an Adrenergic Blocker, Suppresses Melanin Synthesis by Inhibiting the cAMP/CREB Signaling Pathway in Human Melanocytes and Ex Vivo Human Skin Culture.International journal of molecular sciences · 2020Article
- Review 2: Primary graft dysfunction after lung transplant-pathophysiology, clinical considerations and therapeutic targets.Journal of anesthesia · 2020Review
- Pharmacogenomics of Hypertension Treatment.International journal of molecular sciences · 2020Review
- Luteolin Partially Inhibits LFA-1 Expression in Neutrophils Through the ERK Pathway.Inflammation · 2019Article
- Pharmacogenomics And Hypertension: Current Insights.Pharmacogenomics and personalized medicine · 2019Review
- Leukotriene BExperimental & molecular medicine · 2017Article
- Noncanonical regulation of insulin-mediated ERK activation by phosphoinositide 3-kinase γ.Molecular biology of the cell · 2017Article
- Hypertension pharmacogenomics: in search of personalized treatment approaches.Nature reviews. Nephrology · 2016Review
- Association between Beta Adrenergic Receptor Polymorphism and Ischemic Stroke: A Meta-Analysis.Journal of stroke · 2015Review
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Authors and funding
2 authors at 1 institution in 1 country.
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Abstract
Two functionally important β1-adrenergic receptor (β1AR) polymorphisms have been identified. The R389G polymorphism influences coupling to the Gs-cAMP pathway. R(389)-β1ARs display enhanced activation of cAMP/PKA; they provide short-term inotropic support but also cause a predisposition to cardiomyopathic decompensation. A second S49G polymorphism is implicated in the evolution of heart failure, but the mechanism remains uncertain. This study shows that position 49 and 389 polymorphisms function in a coordinate manner to influence agonist-dependent cAMP/PKA and ERK responses. cAMP/PKA and ERK responses are more robust in HEK293 cells that heterologously overexpress G(49)-β1ARs, compared with S(49)-β1ARs. However, this phenotype is most obvious on a G(389)-β1AR background; the more robust agonist-dependent cAMP/PKA and ERK responses in R(389)-β1AR cells effectively obscure the effect of the S49G polymorphism. We also show that isoproterenol (Iso) and carvedilol activate ERK via a similar EGFR-independent mechanism in cells expressing various β1AR haplotypes. However, Iso activates ERK via an Src-independent pathway, but carvedilol-dependent ERK activation requires Src. Since the S49G polymorphism has been linked to changes in β1AR trafficking, we examined whether β1AR polymorphisms influence partitioning to lipid raft membranes. Biochemical fractionation studies show that all four β1AR variants are recovered in buoyant flotillin-enriched membranes; the distinct signaling phenotypes of the different β1AR variants could not be attributed to any gross differences in basal compartmentalization to lipid raft membranes. The allele-specific differences in β1AR signaling phenotypes identified in this study could underlie interindividual differences in responsiveness to β-blocker therapy and clinical outcome in heart failure.
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