ArticleScience (New York, N.Y.)2018
In vivo brain GPCR signaling elucidated by phosphoproteomics.
Article in Science (New York, N.Y.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
66 citing papers in PubMed, 125 citations in OpenAlex.
- Proteomic investigation of signaling dynamics: from static maps to network rewiring.Bioscience reports · 2026Review
- Amino acid balancing and microalgal proteins (Spirulina) improve production performance and milk quality in dairy cows under low-protein diets.NPJ science of food · 2026Article
- A comprehensive proteome and phosphoproteome atlas across nine organs of the Chinese hamster.Animal models and experimental medicine · 2026Article
- An engineered nanobody inhibitor for molecular-to-circuit control of opioid receptor function.bioRxiv : the preprint server for biology · 2026Article
- Applications and Prospects of Artificial Intelligence in ProteomicsCurrent protein & peptide science · 2026Review
- Time-of-day effects on post-exercise phosphoproteomic profiling in mouse hippocampus.Frontiers in cell and developmental biology · 2026Article
- Sleep prevents brain phosphoproteome disruption to safeguard survival.Cell discovery · 2025Article
- Pharmacological characterization of the novel selective kappa opioid receptor agonists 10-Iodo-Akuammicine and 10-Bromo-akuammicine in mice.Neuropharmacology · 2025Article
- Neurons as Immunomodulators: From Rapid Neural Activity to Prolonged Regulation of Cytokines and Microglia.Annual review of biomedical engineering · 2025Review
- Deletion of β-arrestin 2 in mice affects kappa opioid receptor-mediated behaviors depending on sex, ovariectomy status, and behavioral endpoints.Neuroscience letters · 2025Article
- The Dynorphin/-Opioid Receptor System at the Interface of Hyperalgesia/Hyperkatifeia and Addiction.Current addiction reports · 2025Review
- Limitations and potential of κOR biased agonists for pain and itch management.Neuropharmacology · 2024Review
- Genome-wide pan-GPCR cell libraries accelerate drug discovery.Acta pharmaceutica Sinica. B · 2024Review
- Oxa-Iboga alkaloids lack cardiac risk and disrupt opioid use in animal models.Nature communications · 2024Article
- µPhos: a scalable and sensitive platform for high-dimensional phosphoproteomics.Molecular systems biology · 2024Article
- Emerging modes of regulation of neuromodulatory G protein-coupled receptors.Trends in neurosciences · 2024Review
- Article
- Structure-function relationship of dynorphin B variants using naturally occurring amino acid substitutions.Frontiers in pharmacology · 2024Article
- Article
- Subcellular location defines GPCR signal transduction.Science advances · 2023Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
Abstract
A systems view of G protein-coupled receptor (GPCR) signaling in its native environment is central to the development of GPCR therapeutics with fewer side effects. Using the kappa opioid receptor (KOR) as a model, we employed high-throughput phosphoproteomics to investigate signaling induced by structurally diverse agonists in five mouse brain regions. Quantification of 50,000 different phosphosites provided a systems view of KOR in vivo signaling, revealing novel mechanisms of drug action. Thus, we discovered enrichment of the mechanistic target of rapamycin (mTOR) pathway by U-50,488H, an agonist causing aversion, which is a typical KOR-mediated side effect. Consequently, mTOR inhibition during KOR activation abolished aversion while preserving beneficial antinociceptive and anticonvulsant effects. Our results establish high-throughput phosphoproteomics as a general strategy to investigate GPCR in vivo signaling, enabling prediction and modulation of behavioral outcomes.
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Identifiers
What OpenQuestion holds
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.