ArticleProceedings of the National Academy of Sciences of the United States of America2020
Phosphorylation barcode-dependent signal bias of the dopamine D1 receptor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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.
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
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- The Signaling and Pharmacology of the Dopamine D1 Receptor.Frontiers in cellular neuroscience · 2021Pooled it
- Arrestins as programmable integrators of GPCR signaling: structural microstates, spatiotemporal logic, and therapeutic control.Cell discovery · 2026Review
- Intrinsic conformational equilibria position arrestin-2 for activation.Protein science : a publication of the Protein Society · 2026Article
- Mechanism of beta-arrestin 1 mediated Src activation via Src SH3 domain revealed by cryo-electron microscopy.Nature communications · 2026Article
- Distinct membrane binding properties of the two non-visual arrestins.Communications biology · 2026Article
- Phosphorylation induces altered protonation states and allosterically regulates Rac1-RhoGDI complex.Protein science : a publication of the Protein Society · 2026Article
- Intrinsic conformational equilibria position arrestin-2 for activation.bioRxiv : the preprint server for biology · 2025Article
- Article
- Mechanism of beta-arrestin 1 mediated Src activation via Src SH3 domain revealed by cryo-electron microscopy.bioRxiv : the preprint server for biology · 2025Article
- An arginine switch drives the stepwise activation of β-arrestin by CXCR7.PLoS biology · 2025Article
- Genetic variants of accessory proteins and G proteins in human genetic disease.Critical reviews in clinical laboratory sciences · 2025Review
- Molecular mechanism of β-arrestin-2 pre-activation by phosphatidylinositol 4,5-bisphosphate.EMBO reports · 2024Article
- Phosphorylation patterns in the AT1R C-terminal tail specify distinct downstream signaling pathways.Science signaling · 2024Article
- GPCR-dependent and -independent arrestin signaling.Trends in pharmacological sciences · 2024Review
- Arrestins: A Small Family of Multi-Functional Proteins.International journal of molecular sciences · 2024Review
- How New Developments in Pharmacology Receptor Theory Are Changing (Our Understanding of) Hypertension Therapy.American journal of hypertension · 2024Review
- GPCR kinases differentially modulate biased signaling downstream of CXCR3 depending on their subcellular localization.Science signaling · 2024Article
- ACKR3 Proximity Labeling Identifies Novel G protein- and β-arrestin-independent GPCR Interacting Proteins.bioRxiv : the preprint server for biology · 2024Article
- Phosphorylation bar-coding of free fatty acid receptor 2 is generated in a tissue-specific manner.eLife · 2023Article
- The Role of Retinal Dopamine D1 Receptors in Ocular Growth and Myopia Development in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Agonist-activated G protein-coupled receptors (GPCRs) must correctly select from hundreds of potential downstream signaling cascades and effectors. To accomplish this, GPCRs first bind to an intermediary signaling protein, such as G protein or arrestin. These intermediaries initiate signaling cascades that promote the activity of different effectors, including several protein kinases. The relative roles of G proteins versus arrestins in initiating and directing signaling is hotly debated, and it remains unclear how the correct final signaling pathway is chosen given the ready availability of protein partners. Here, we begin to deconvolute the process of signal bias from the dopamine D1 receptor (D1R) by exploring factors that promote the activation of ERK1/2 or Src, the kinases that lead to cell growth and proliferation. We found that ERK1/2 activation involves both arrestin and Gαs, while Src activation depends solely on arrestin. Interestingly, we found that the phosphorylation pattern influences both arrestin and Gαs coupling, suggesting an additional way the cells regulate G protein signaling. The phosphorylation sites in the D1R intracellular loop 3 are particularly important for directing the binding of G protein versus arrestin and for selecting between the activation of ERK1/2 and Src. Collectively, these studies correlate functional outcomes with a physical basis for signaling bias and provide fundamental information on how GPCR signaling is directed.
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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.