ArticleThe Journal of biological chemistry2011
The beta-arrestin pathway-selective type 1A angiotensin receptor (AT1A) agonist [Sar1,Ile4,Ile8]angiotensin II regulates a robust G protein-independent signaling network.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 69 citations in OpenAlex.
- Phosphoproteomics for studying signaling pathways evoked by hormones of the renin-angiotensin system: A source of untapped potential.Acta physiologica (Oxford, England) · 2025Review
- How New Developments in Pharmacology Receptor Theory Are Changing (Our Understanding of) Hypertension Therapy.American journal of hypertension · 2024Review
- Myogenic Vasoconstriction Requires Canonical GJournal of the American Heart Association · 2022Article
- Intrinsic bias at non-canonical, β-arrestin-coupled seven transmembrane receptors.Molecular cell · 2021Article
- Targeting the Angiotensin II Type 1 Receptor in Cerebrovascular Diseases: Biased Signaling Raises New Hopes.International journal of molecular sciences · 2021Review
- The Role of β-Arrestin Proteins in Organization of Signaling and Regulation of the AT1 Angiotensin Receptor.Frontiers in endocrinology · 2019Review
- Tonic ATP-mediated growth suppression in peripheral nerve glia requires arrestin-PP2 and is evaded in NF1.Acta neuropathologica communications · 2018Article
- Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology.Physiological reviews · 2018Review
- In vivo brain GPCR signaling elucidated by phosphoproteomics.Science (New York, N.Y.) · 2018Article
- Novel regulations of the angiotensin II receptor type 1 by calmodulin.Biochemical pharmacology · 2018Article
- GnRH regulates the expression of its receptor accessory protein SET in pituitary gonadotropes.PloS one · 2018Article
- Translating in vitro ligand bias into in vivo efficacy.Cellular signalling · 2018Review
- Barcoding of GPCR trafficking and signaling through the various trafficking roadmaps by compartmentalized signaling networks.Cellular signalling · 2017Review
- The Diverse Roles of Arrestin Scaffolds in G Protein-Coupled Receptor Signaling.Pharmacological reviews · 2017Review
- Regulation of arterial reactivity by concurrent signaling through the E-prostanoid receptor 3 and angiotensin receptor 1.Vascular pharmacology · 2016Article
- Angiotensin II receptors and peritoneal dialysis-induced peritoneal fibrosis.The international journal of biochemistry & cell biology · 2016Review
- Exploring G protein-coupled receptor signaling networks using SILAC-based phosphoproteomics.Methods (San Diego, Calif.) · 2016Article
- Informatic deconvolution of biased GPCR signaling mechanisms from in vivo pharmacological experimentation.Methods (San Diego, Calif.) · 2016Article
- International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli [corrected].Pharmacological reviews · 2015Review
- Fulfilling the Promise of "Biased" G Protein-Coupled Receptor Agonism.Molecular pharmacology · 2015Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The angiotensin II peptide analog [Sar(1),Ile(4),Ile(8)]AngII (SII) is a biased AT(1A) receptor agonist that stimulates receptor phosphorylation, β-arrestin recruitment, receptor internalization, and β-arrestin-dependent ERK1/2 activation without activating heterotrimeric G-proteins. To determine the scope of G-protein-independent AT(1A) receptor signaling, we performed a gel-based phosphoproteomic analysis of AngII and SII-induced signaling in HEK cells stably expressing AT(1A) receptors. A total of 34 differentially phosphorylated proteins were detected, of which 16 were unique to SII and eight to AngII stimulation. MALDI-TOF/TOF mass fingerprinting was employed to identify 24 SII-sensitive phosphoprotein spots, of which three (two peptide inhibitors of protein phosphatase 2A (I1PP2A and I2PP2A) and prostaglandin E synthase 3 (PGES3)) were selected for validation and further study. We found that phosphorylation of I2PP2A was associated with rapid and transient inhibition of a β-arrestin 2-associated pool of protein phosphatase 2A, leading to activation of Akt and increased phosphorylation of glycogen synthase kinase 3β in an arrestin signalsome complex. SII-stimulated PGES3 phosphorylation coincided with an increase in β-arrestin 1-associated PGES3 and an arrestin-dependent increase in cyclooxygenase 1-dependent prostaglandin E(2) synthesis. These findings suggest that AT(1A) receptors regulate a robust G protein-independent signaling network that affects protein phosphorylation and autocrine/paracrine prostaglandin production and that these pathways can be selectively modulated by biased ligands that antagonize G protein activation.
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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.