ArticleThe Journal of cell biology2000
beta-arrestin-dependent endocytosis of proteinase-activated receptor 2 is required for intracellular targeting of activated ERK1/2.
Article in The Journal of cell biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 331 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
331 citing papers in PubMed, 1 synthesis or guideline pooled it, 806 citations in OpenAlex.
- Characterization and Functions of Protease-Activated Receptor 2 in Obesity, Diabetes, and Metabolic Syndrome: A Systematic Review.BioMed research international · 2016Pooled it
- Protease-Activated Receptor-2 as a Proteolytic Rheostat in Colorectal and Pancreatic Cancer: From Mechanism to Biomarker-Guided Therapy.International journal of molecular sciences · 2026Review
- The prenylated pUS2 protein of pseudorabies virus contributes to phosphorylation of connexin 43 and suppression of gap junctional intercellular communication.Journal of virology · 2026Article
- Article
- PAR2-β-arrestin 2-ERK axis mediatesiScience · 2026Article
- MMP1 and PRSS23 induce PARCommunications biology · 2026Article
- Adhesion G protein-coupled receptors.Pharmacological reviews · 2026Review
- Cooperative Control of Arrestin Activation By Membrane Lipids And Phosphorylation Barcodes.bioRxiv : the preprint server for biology · 2026Article
- Mast Cells and Substance P: Neuroinflammatory Loops at the Molecular and Translational Clinical Levels.Biomolecules · 2026Review
- Protease-Activated Receptor-2 Promotes Metastasis: An Emerging Therapeutic Target.Molecular cancer research : MCR · 2026Review
- Phosphoregulation of the novel hemi-arrestin MAPK scaffold Sms1 prevents untimely mating.Nature communications · 2026Article
- Protease-activated receptors act as a liaison between metabolism and inflammation.Inflammopharmacology · 2026Review
- Modulation of Nociceptive Ion Channels by Protease-Activated Receptor-2 in Inflammatory Pain: Molecular Mechanisms and Therapeutic Potential.International journal of molecular sciences · 2026Review
- Integrated airway epithelial signaling networks linking allergen-driven inflammation to airway remodeling in asthma.Frontiers in immunology · 2026Review
- Mechanisms of Location Bias in G Protein-Coupled Receptors.Handbook of experimental pharmacology · 2026Review
- α, δ‑ACS pharmacology & translational science · 2025Article
- Nanomedicines targeting protease-activated receptor 2 in endosomes provide sustained analgesia.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- An arginine switch drives the stepwise activation of β-arrestin by CXCR7.PLoS biology · 2025Article
- Biased agonism of G protein-coupled receptors as a novel strategy for osteoarthritis therapy.Bone research · 2025Review
271 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
6 authors at 1 institution in 1 country.
Funding
Abstract
Recently, a requirement for beta-arrestin-mediated endocytosis in the activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) by several G protein-coupled receptors (GPCRs) has been proposed. However, the importance of this requirement for function of ERK1/2 is unknown. We report that agonists of Galphaq-coupled proteinase-activated receptor 2 (PAR2) stimulate formation of a multiprotein signaling complex, as detected by gel filtration, immunoprecipitation and immunofluorescence. The complex, which contains internalized receptor, beta-arrestin, raf-1, and activated ERK, is required for ERK1/2 activation. However, ERK1/2 activity is retained in the cytosol and neither translocates to the nucleus nor causes proliferation. In contrast, a mutant PAR2 (PAR2deltaST363/6A), which is unable to interact with beta-arrestin and, thus, does not desensitize or internalize, activates ERK1/2 by a distinct pathway, and fails to promote both complex formation and cytosolic retention of the activated ERK1/2. Whereas wild-type PAR2 activates ERK1/2 by a PKC-dependent and probably a ras-independent pathway, PAR2(deltaST363/6A) appears to activate ERK1/2 by a ras-dependent pathway, resulting in increased cell proliferation. Thus, formation of a signaling complex comprising PAR2, beta-arrestin, raf-1, and activated ERK1/2 might ensure appropriate subcellular localization of PAR2-mediated ERK activity, and thereby determine the mitogenic potential of receptor agonists.
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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.