ArticleThe Journal of biological chemistry2009
Endosomal deubiquitinating enzymes control ubiquitination and down-regulation of protease-activated receptor 2.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
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The trial behind it
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Who cites it
54 citing papers in PubMed, 79 citations in OpenAlex.
- 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
- Protease-Activated Receptor-2 Promotes Metastasis: An Emerging Therapeutic Target.Molecular cancer research : MCR · 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
- Selective Modulation of PAR-2-Driven Inflammatory Pathways by Oleocanthal: Attenuation of TNF-α and Calcium Dysregulation in Colorectal Cancer Models.International journal of molecular sciences · 2025Article
- USP34 regulates endothelial PAR1 mRNA transcript expression and cellular signaling.Molecular biology of the cell · 2025Article
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- Structural and Functional Basis of JAMM Deubiquitinating Enzymes in Disease.Biomolecules · 2022Review
- Post-Translational Modifications of G Protein-Coupled Receptors Control Cellular Signaling Dynamics in Space and Time.Pharmacological reviews · 2021Review
- Agonist-activated glucagon receptors are deubiquitinated at early endosomes by two distinct deubiquitinases to facilitate Rab4a-dependent recycling.The Journal of biological chemistry · 2020Article
- Ubiquitin-specific protease 8 (USP8/UBPy): a prototypic multidomain deubiquitinating enzyme with pleiotropic functions.Biochemical Society transactions · 2019Review
- Endo-lysosomal sorting of G-protein-coupled receptors by ubiquitin: Diverse pathways for G-protein-coupled receptor destruction and beyond.Traffic (Copenhagen, Denmark) · 2019Review
- Membrane-Anchored Serine Proteases and Protease-Activated Receptor-2-Mediated Signaling: Co-Conspirators in Cancer Progression.Cancer research · 2019Review
- Zika virus elicits inflammation to evade antiviral response by cleaving cGAS via NS1-caspase-1 axis.The EMBO journal · 2018Article
- GPCRs in Cancer: Protease-Activated Receptors, Endocytic Adaptors and Signaling.International journal of molecular sciences · 2018Review
- The Role of Ubiquitination and Hepatocyte Growth Factor-Regulated Tyrosine Kinase Substrate in the Degradation of the Adrenomedullin Type I Receptor.Scientific reports · 2017Article
- Regulation of G Protein-Coupled Receptors by Ubiquitination.International journal of molecular sciences · 2017Review
- A functional endosomal pathway is necessary for lysosome biogenesis in Drosophila.BMC cell biology · 2016Article
- PAR2-dependent activation of GSK3β regulates the survival of colon stem/progenitor cells.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- The Endosome-associated Deubiquitinating Enzyme USP8 Regulates BACE1 Enzyme Ubiquitination and Degradation.The Journal of biological chemistry · 2016Article
- The emerging role of deubiquitinating enzymes in genomic integrity, diseases, and therapeutics.Cell & bioscience · 2016Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The E3 ubiquitin ligase c-Cbl ubiquitinates the G protein-coupled receptor protease-activated receptor 2 (PAR(2)), which is required for postendocytic sorting of activated receptors to lysosomes, where degradation terminates signaling. The mechanisms of PAR(2) deubiquitination and its importance in trafficking and signaling of endocytosed PAR(2) are unknown. We report that receptor deubiquitination occurs between early endosomes and lysosomes and involves the endosomal deubiquitinating proteases AMSH and UBPY. Expression of the catalytically inactive mutants, AMSH(D348A) and UBPY(C786S), caused an increase in PAR(2) ubiquitination and trapped the receptor in early endosomes, thereby preventing lysosomal trafficking and degradation. Small interfering RNA knockdown of AMSH or UBPY also impaired deubiquitination, lysosomal trafficking, and degradation of PAR(2). Trapping PAR(2) in endosomes through expression of AMSH(D348A) or UBPY(C786S) did not prolong the association of PAR(2) with beta-arrestin2 or the duration of PAR(2)-induced ERK2 activation. Thus, AMSH and UBPY are essential for trafficking and down-regulation of PAR(2) but not for regulating PAR(2) dissociation from beta-arrestin2 or PAR(2)-mediated ERK2 activation.
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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.