ArticleThe Journal of biological chemistry2014
Arrestin-dependent angiotensin AT1 receptor signaling regulates Akt and mTor-mediated protein synthesis.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 45 citations in OpenAlex.
- The onset of hypertension in metabolic syndrome is independent of renal sympathetic innervation.Life science alliance · 2026Article
- Role of β-Arrestin2 Signaling in Neuropharmacological Effects of Psychedelic Drugs.ACS chemical neuroscience · 2026Article
- Genetic Deletion of β-Arrestin 2 From the Subfornical Organ and Other Periventricular Nuclei in the Brain Alters Fluid Homeostasis and Blood Pressure.Hypertension (Dallas, Tex. : 1979) · 2024Article
- β-adrenergic receptor signaling mediated by β-arrestins and its potential role in heart failure.Current opinion in physiology · 2024Article
- Receptor expression and signaling properties in the brain, and structural ligand motifs that contribute to delta opioid receptor agonist-induced seizures.Neuropharmacology · 2023Review
- Exploration of beta-arrestin isoform signaling pathways in delta opioid receptor agonist-induced convulsions.Frontiers in pharmacology · 2022Article
- Beta-Arrestins in the Treatment of Heart Failure Related to Hypertension: A Comprehensive Review.Pharmaceutics · 2021Review
- Biased ligands at opioid receptors: Current status and future directions.Science signaling · 2021Review
- Acetylation-dependent glutamate receptor GluR signalosome formation for STAT3 activation in both transcriptional and metabolism regulation.Cell death discovery · 2021Article
- Targeting Molecular Mechanism of Vascular Smooth Muscle Senescence Induced by Angiotensin II, A Potential Therapy via Senolytics and Senomorphics.International journal of molecular sciences · 2020Review
- Investigating higher-order interactions in single-cell data with scHOT.Nature methods · 2020Article
- Review
- The ATRQβ-001 vaccine improves cardiac function and prevents postinfarction cardiac remodeling in mice.Hypertension research : official journal of the Japanese Society of Hypertension · 2019Article
- Manifold roles of β-arrestins in GPCR signaling elucidated with siRNA and CRISPR/Cas9.Science signaling · 2018Article
- GPCRs in pulmonary arterial hypertension: tipping the balance.British journal of pharmacology · 2018Review
- Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology.Physiological reviews · 2018Review
- Biased signalling: from simple switches to allosteric microprocessors.Nature reviews. Drug discovery · 2018Review
- The Role of G Protein-Coupled Receptors in the Right Ventricle in Pulmonary Hypertension.Frontiers in cardiovascular medicine · 2018Review
- Distinct Signaling Patterns of Allosteric Antagonism at the P2YMolecular pharmacology · 2017Article
- AT1 receptor signaling pathways in the cardiovascular system.Pharmacological research · 2017Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Control of protein synthesis is critical to both cell growth and proliferation. The mammalian target of rapamycin (mTOR) integrates upstream growth, proliferation, and survival signals, including those transmitted via ERK1/2 and Akt, to regulate the rate of protein translation. The angiotensin AT1 receptor has been shown to activate both ERK1/2 and Akt in arrestin-based signalsomes. Here, we examine the role of arrestin-dependent regulation of ERK1/2 and Akt in the stimulation of mTOR-dependent protein translation by the AT1 receptor using HEK293 and primary vascular smooth muscle cell models. Nascent protein synthesis stimulated by both the canonical AT1 receptor agonist angiotensin II (AngII), and the arrestin pathway-selective agonist [Sar(1)-Ile(4)-Ile(8)]AngII (SII), is blocked by shRNA silencing of βarrestin1/2 or pharmacological inhibition of Akt, ERK1/2, or mTORC1. In HEK293 cells, SII activates a discrete arrestin-bound pool of Akt and promotes Akt-dependent phosphorylation of mTOR and its downstream effector p70/p85 ribosomal S6 kinase (p70/85S6K). In parallel, SII-activated ERK1/2 helps promote mTOR and p70/85S6K phosphorylation, and is required for phosphorylation of the known ERK1/2 substrate p90 ribosomal S6 kinase (p90RSK). Thus, arrestins coordinate AT1 receptor regulation of ERK1/2 and Akt activity and stimulate protein translation via both Akt-mTOR-p70/85S6K and ERK1/2-p90RSK pathways. These results suggest that in vivo, arrestin pathway-selective AT1 receptor agonists may promote cell growth or hypertrophy through arrestin-mediated mechanisms despite their antagonism of G protein signaling.
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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.