ArticleThe Journal of cell biology2015
Ubiquitin plays an atypical role in GPCR-induced p38 MAP kinase activation on endosomes.
Article in The Journal of cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 79 citations in OpenAlex.
- Cannabinoid tolerance relies on CBProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Signaling bias of the protease-activated receptor-1 is dictated by distinct GRK5 and β-arrestin-2 determinants.Cell reports · 2026Article
- Activated protein C drives β-arrestin-2- and c-Src-dependent phosphorylation of Cav1 and modulates Cav1 association with PAR1 and GRK5.The Journal of biological chemistry · 2026Article
- Unanchored K63-linked polyubiquitin chains: a novel second messenger involved in G protein-coupled receptors early signaling events.Cell communication and signaling : CCS · 2026Article
- Atypical p38 Kinase Signaling in Retinal Vascular Damage and Recovery.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Role of Atypical MAPK p38 Signaling in the Progression of Influenza A-Induced Acute Lung Injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Protease-Activated Receptors (PARs): Biology and Therapeutic Potential in Perioperative Stroke.Translational stroke research · 2025Review
- USP34 regulates endothelial PAR1 mRNA transcript expression and cellular signaling.Molecular biology of the cell · 2025Article
- Ubiquitin-driven G protein-coupled receptor inflammatory signaling at the endosome.American journal of physiology. Cell physiology · 2024Review
- The implications of exercise in Drosophila melanogaster: insights into Akt/p38 MAPK/Nrf2 pathway associated with Hsp70 regulation in redox balance maintenance.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2023Article
- P38 kinase in gastrointestinal cancers.Cancer gene therapy · 2023Review
- Divergent regulation of α-arrestin ARRDC3 function by ubiquitination.Molecular biology of the cell · 2023Article
- Fluorescence resonance energy transfer (FRET) spatiotemporal mapping of atypical P38 reveals an endosomal and cytosolic spatial bias.Scientific reports · 2023Article
- Regulation of MAPK Signaling Pathways by the Large HERC Ubiquitin Ligases.International journal of molecular sciences · 2023Review
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- Heat shock protein 27 activity is linked to endothelial barrier recovery after proinflammatory GPCR-induced disruption.Science signaling · 2021Article
- Compartmentalized GPCR Signaling from Intracellular Membranes.The Journal of membrane biology · 2021Review
- Atypical p38 Signaling, Activation, and Implications for Disease.International journal of molecular sciences · 2021Review
- Development of a Novel SNAP-Epitope Tag/Near-Infrared Imaging Assay to Quantify G Protein-Coupled Receptor Degradation in Human Cells.SLAS discovery : advancing life sciences R & D · 2021Article
- Subcellular hot spots of GPCR signaling promote vascular inflammation.Current opinion in endocrine and metabolic research · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Protease-activated receptor 1 (PAR1) is a G protein-coupled receptor (GPCR) for thrombin and promotes inflammatory responses through multiple pathways including p38 mitogen-activated protein kinase signaling. The mechanisms that govern PAR1-induced p38 activation remain unclear. Here, we define an atypical ubiquitin-dependent pathway for p38 activation used by PAR1 that regulates endothelial barrier permeability. Activated PAR1 K63-linked ubiquitination is mediated by the NEDD4-2 E3 ubiquitin ligase and initiated recruitment of transforming growth factor-β-activated protein kinase-1 binding protein-2 (TAB2). The ubiquitin-binding domain of TAB2 was essential for recruitment to PAR1-containing endosomes. TAB2 associated with TAB1, which induced p38 activation independent of MKK3 and MKK6. The P2Y1 purinergic GPCR also stimulated p38 activation via NEDD4-2-mediated ubiquitination and TAB1-TAB2. TAB1-TAB2-dependent p38 activation was critical for PAR1-promoted endothelial barrier permeability in vitro, and p38 signaling was required for PAR1-induced vascular leakage in vivo. These studies define an atypical ubiquitin-mediated signaling pathway used by a subset of GPCRs that regulates endosomal p38 signaling and endothelial barrier disruption.
Indexed as
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.