ArticleMolecular systems biology2012
Competing G protein-coupled receptor kinases balance G protein and β-arrestin signaling.
Article in Molecular systems biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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
33 citing papers in PubMed, 75 citations in OpenAlex.
- Spatiotemporal modeling of GPCR signaling: The role of endosomal dynamics and receptor recycling.PLoS computational biology · 2026Article
- G protein-coupled receptor signaling: transducers and effectors.American journal of physiology. Cell physiology · 2022Review
- Selective Signal Capture from Multidimensional GPCR Outputs with Biased Agonists: Progress Towards Novel Drug Development.Molecular diagnosis & therapy · 2022Review
- Biased β-Agonists Favoring Gs over β-Arrestin for Individualized Treatment of Obstructive Lung Disease.Journal of personalized medicine · 2022Review
- GPCR kinase knockout cells reveal the impact of individual GRKs on arrestin binding and GPCR regulation.Nature communications · 2022Article
- Identification and characterization of an atypical Gαs-biased βProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Review
- In Vitro Impact of FSH Glycosylation Variants on FSH Receptor-stimulated Signal Transduction and Functional Selectivity.Journal of the Endocrine Society · 2020Article
- Differential Role of Serines and Threonines in Intracellular Loop 3 and C-Terminal Tail of the Histamine HACS pharmacology & translational science · 2020Article
- Follicle-stimulating Hormone (FSH) Action on Spermatogenesis: A Focus on Physiological and Therapeutic Roles.Journal of clinical medicine · 2020Review
- The road to ERK activation: Do neurons take alternate routes?Cellular signalling · 2020Review
- New Routes in GPCR/β-Arrestin-Driven Signaling in Cancer Progression and Metastasis.Frontiers in pharmacology · 2019Review
- Biased Signaling and Allosteric Modulation at the FSHR.Frontiers in endocrinology · 2019Review
- β-arrestin-biased agonism of β-adrenergic receptor regulates Dicer-mediated microRNA maturation to promote cardioprotective signaling.Journal of molecular and cellular cardiology · 2018Article
- The Role of G Protein-coupled Receptor Kinases in Cancer.International journal of biological sciences · 2018Review
- Tamoxifen-Induced Apoptosis of MCF-7 Cells via GPR30/PI3K/MAPKs Interactions: Verification by ODE Modeling and RNA Sequencing.Frontiers in physiology · 2018Article
- A Comprehensive View of the β-Arrestinome.Frontiers in endocrinology · 2017Article
- The analysis of heterotaxy patients reveals new loss-of-function variants of GRK5.Scientific reports · 2016Article
- Impedance-based analysis of mu opioid receptor signaling and underlying mechanisms.Biochemistry and biophysics reports · 2016Article
- Qualitative dynamics semantics for SBGN process description.BMC systems biology · 2016Article
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
Seven-transmembrane receptors (7TMRs) are involved in nearly all aspects of chemical communications and represent major drug targets. 7TMRs transmit their signals not only via heterotrimeric G proteins but also through β-arrestins, whose recruitment to the activated receptor is regulated by G protein-coupled receptor kinases (GRKs). In this paper, we combined experimental approaches with computational modeling to decipher the molecular mechanisms as well as the hidden dynamics governing extracellular signal-regulated kinase (ERK) activation by the angiotensin II type 1A receptor (AT(1A)R) in human embryonic kidney (HEK)293 cells. We built an abstracted ordinary differential equations (ODE)-based model that captured the available knowledge and experimental data. We inferred the unknown parameters by simultaneously fitting experimental data generated in both control and perturbed conditions. We demonstrate that, in addition to its well-established function in the desensitization of G-protein activation, GRK2 exerts a strong negative effect on β-arrestin-dependent signaling through its competition with GRK5 and 6 for receptor phosphorylation. Importantly, we experimentally confirmed the validity of this novel GRK2-dependent mechanism in both primary vascular smooth muscle cells naturally expressing the AT(1A)R, and HEK293 cells expressing other 7TMRs.
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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.