ArticleProceedings of the National Academy of Sciences of the United States of America2010
Global phosphorylation analysis of beta-arrestin-mediated signaling downstream of a seven transmembrane receptor (7TMR).
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 99 papers.
What it found
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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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Who cites it
99 citing papers in PubMed, 188 citations in OpenAlex.
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- GPCR Biased Signaling in Cancer.Handbook of experimental pharmacology · 2026Review
- Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) for Quantitative Proteomics.Advances in experimental medicine and biology · 2026Review
- Regulation of CXCR4 function by S1PCell communication and signaling : CCS · 2025Article
- Phosphoproteomics for studying signaling pathways evoked by hormones of the renin-angiotensin system: A source of untapped potential.Acta physiologica (Oxford, England) · 2025Review
- Phosphorylation regulates the chromatin remodeler SMARCAD1 in nucleosome binding, ATP hydrolysis, and histone exchange.The Journal of biological chemistry · 2024Article
- Comprehensive Analysis of Kisspeptin Signaling: Effects on Cellular Dynamics in Cervical Cancer.Biomolecules · 2024Article
- G Protein-Coupled Receptors: A Century of Research and Discovery.Circulation research · 2024Review
- GPCR kinases differentially modulate biased signaling downstream of CXCR3 depending on their subcellular localization.Science signaling · 2024Article
- Activation of GPR3-β-arrestin2-PKM2 pathway in Kupffer cells stimulates glycolysis and inhibits obesity and liver pathogenesis.Nature communications · 2024Article
- Article
- Altered CXCR4 dynamics at the cell membrane impairs directed cell migration in WHIM syndrome patients.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Identification and characterization of an atypical Gαs-biased βProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Intrinsic bias at non-canonical, β-arrestin-coupled seven transmembrane receptors.Molecular cell · 2021Article
- Dendritic cell migration in inflammation and immunity.Cellular & molecular immunology · 2021Review
- A cellular perspective of bias at G protein-coupled receptors.Protein science : a publication of the Protein Society · 2020Review
- βarrestin-1 regulates DNA repair by acting as an E3-ubiquitin ligase adaptor for 53BP1.Cell death and differentiation · 2020Article
- The Effect of Cell Surface Expression and Linker Sequence on the Recruitment of Arrestin to the GIP Receptor.Frontiers in pharmacology · 2020Article
- Structure and function of β-arrestins, their emerging role in breast cancer, and potential opportunities for therapeutic manipulation.Advances in cancer research · 2020Article
- Design and characterization of mutant and wildtype huntingtin proteins produced from a toolkit of scalable eukaryotic expression systems.The Journal of biological chemistry · 2019Article
39 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
Abstract
beta-Arrestin-mediated signaling downstream of seven transmembrane receptors (7TMRs) is a relatively new paradigm for signaling by these receptors. We examined changes in protein phosphorylation occurring when HEK293 cells expressing the angiotensin II type 1A receptor (AT1aR) were stimulated with the beta-arrestin-biased ligand Sar(1), Ile(4), Ile(8)-angiotensin (SII), a ligand previously found to signal through beta-arrestin-dependent, G protein-independent mechanisms. Using a phospho-antibody array containing 46 antibodies against signaling molecules, we found that phosphorylation of 35 proteins increased upon SII stimulation. These SII-mediated phosphorylation events were abrogated after depletion of beta-arrestin 2 through siRNA-mediated knockdown. We also performed an MS-based quantitative phosphoproteome analysis after SII stimulation using a strategy of stable isotope labeling of amino acids in cell culture (SILAC). We identified 1,555 phosphoproteins (4,552 unique phosphopeptides), of which 171 proteins (222 phosphopeptides) showed increased phosphorylation, and 53 (66 phosphopeptides) showed decreased phosphorylation upon SII stimulation of the AT1aR. This study identified 38 protein kinases and three phosphatases whose phosphorylation status changed upon SII treatment. Using computational approaches, we performed system-based analyses examining the beta-arrestin-mediated phosphoproteome including construction of a kinase-substrate network for beta-arrestin-mediated AT1aR signaling. Our analysis demonstrates that beta-arrestin-dependent signaling processes are more diverse than previously appreciated. Notably, our analysis identifies an AT1aR-mediated cytoskeletal reorganization network whereby beta-arrestin regulates phosphorylation of several key proteins, including cofilin and slingshot. This study provides a system-based view of beta-arrestin-mediated phosphorylation events downstream of a 7TMR and opens avenues for research in a rapidly evolving area of 7TMR 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.