ArticleProceedings of the National Academy of Sciences of the United States of America2008
Beta-blockers alprenolol and carvedilol stimulate beta-arrestin-mediated EGFR transactivation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 151 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
151 citing papers in PubMed, 1 synthesis or guideline pooled it, 275 citations in OpenAlex.
- Improving the preclinical models for the study of chemotherapy-induced cardiotoxicity: a Position Paper of the Italian Working Group on Drug Cardiotoxicity and Cardioprotection.Heart failure reviews · 2015Guideline
- Arrestins as programmable integrators of GPCR signaling: structural microstates, spatiotemporal logic, and therapeutic control.Cell discovery · 2026Review
- Small-molecule modulation of β-arrestins.Nature · 2026Article
- Carvedilol Exerts Cardioprotective Effects Against Doxorubicin Toxicity via Autophagy Modulation and Energetics Restoration.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Signaling bias of the protease-activated receptor-1 is dictated by distinct GRK5 and β-arrestin-2 determinants.Cell reports · 2026Article
- BACH2 links β1-adrenergic receptor/β-arrestin1 signaling to MIAT to inhibit cardiac fibroblast activation and cardiomyocyte apoptosis.Cell death discovery · 2026Article
- Regulation of MRGPRX2-mediated mast cell function by competence-stimulating peptide 1 and pro-adrenomedullin peptide.Frontiers in immunology · 2026Article
- The beta1-adrenergic receptor in the heart.Cell death discovery · 2025Review
- βmedRxiv : the preprint server for health sciences · 2025Article
- An arginine switch drives the stepwise activation of β-arrestin by CXCR7.PLoS biology · 2025Article
- Arrestin recognizes GPCRs independently of the receptor state.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Functional dynamics of G protein-coupled receptors reveal new routes for drug discovery.Nature reviews. Drug discovery · 2025Review
- Cancer-Therapy-Related Cardiac Dysfunction: Latest Advances in Prevention and Treatment.Life (Basel, Switzerland) · 2025Review
- Molecular simulations reveal intricate coupling between agonist-bound β-adrenergic receptors and G protein.iScience · 2025Article
- Functional consequences of spatial, temporal and ligand bias of G protein-coupled receptors.Nature reviews. Nephrology · 2024Review
- Review
- Know your molecule: pharmacological characterization of drug candidates to enhance efficacy and reduce late-stage attrition.Nature reviews. Drug discovery · 2024Review
- The multifaceted role of beta-blockers in overcoming cancer progression and drug resistance: Extending beyond cardiovascular disorders.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- Internalized β2-Adrenergic Receptors Oppose PLC-Dependent Hypertrophic Signaling.Circulation research · 2024Article
- G Protein-Coupled Receptors: A Century of Research and Discovery.Circulation research · 2024Review
91 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Recent evidence suggests that binding of agonist to its cognate receptor initiates not only classical G protein-mediated signaling, but also beta-arrestin-dependent signaling. One such beta-arrestin-mediated pathway uses the beta(1)-adrenergic receptor (beta(1)AR) to transactivate the EGFR. To determine whether beta-adrenergic ligands that do not activate G protein signaling (i.e., beta-blockers) can stabilize the beta(1)AR in a signaling conformation, we screened 20 beta-blockers for their ability to stimulate beta-arrestin-mediated EGFR transactivation. Here we show that only alprenolol (Alp) and carvedilol (Car) induce beta(1)AR-mediated transactivation of the EGFR and downstream ERK activation. By using mutants of the beta(1)AR lacking G protein-coupled receptor kinase phosphorylation sites and siRNA directed against beta-arrestin, we show that Alp- and Car-stimulated EGFR transactivation requires beta(1)AR phosphorylation at consensus G protein-coupled receptor kinase sites and beta-arrestin recruitment to the ligand-occupied receptor. Moreover, pharmacological inhibition of Src and EGFR blocked Alp- and Car-stimulated EGFR transactivation. Our findings demonstrate that Alp and Car are ligands that not only act as classical receptor antagonists, but can also stimulate signaling pathways in a G protein-independent, beta-arrestin-dependent fashion.
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Registered trials
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.