ArticleAmerican journal of physiology. Cell physiology2011
Apical and basolateral pools of proteinase-activated receptor-2 direct distinct signaling events in the intestinal epithelium.
Article in American journal of physiology. Cell physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- Targeting PAR-2 with a negative allosteric modulator increases tumor antigen presentation and potentiates anti-PD-1 immunotherapy.Journal for immunotherapy of cancer · 2026Article
- Proteases in intestinal health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Hereditary α-tryptasemia; a review of mechanisms linking α-tryptase gene dosage to intestinal homeostasis and immunopathology.Frontiers in allergy · 2026Review
- Protease-Activated Receptor 2 Activation Provokes an Increase in Intracellular Calcium and Serotonin Secretion in a Human Enteroendocrine Cell Line.Cell biochemistry and function · 2025Article
- Eimeria: Navigating complex intestinal ecosystems.PLoS pathogens · 2024Review
- Beyond Anticoagulation: A Comprehensive Review of Non-Vitamin K Oral Anticoagulants (NOACs) in Inflammation and Protease-Activated Receptor Signaling.International journal of molecular sciences · 2024Review
- Par2-mediated responses in inflammation and regeneration: choosing between repair and damage.Inflammation and regeneration · 2024Review
- A novel trypsin of Trichinella spiralis mediates larval invasion of gut epithelium via binding to PAR2 and activating ERK1/2 pathway.PLoS neglected tropical diseases · 2024Article
- Article
- Protease-activated receptor-2 activation enhances epithelial wound healing via epidermal growth factor receptor.Tissue barriers · 2022Article
- Modulation of Intestinal Epithelial Permeability via Protease-Activated Receptor-2-Induced Autophagy.Cells · 2022Article
- High Affinity Fluorescent Probe for Proteinase-Activated Receptor 2 (PAR2).ACS medicinal chemistry letters · 2019Article
- Measurement of novel intestinal secretory and barrier pathways and effects of proteases.Neurogastroenterology and motility · 2019Review
- Protease-Activated Receptors in the Intestine: Focus on Inflammation and Cancer.Frontiers in endocrinology · 2019Review
- Decreased TESK1-mediated cofilin 1 phosphorylation in the jejunum of IBS-D patients may explain increased female predisposition to epithelial dysfunction.Scientific reports · 2018Article
- Epigenetic silencing of PRSS3 provides growth and metastasis advantage for human hepatocellular carcinoma.Journal of molecular medicine (Berlin, Germany) · 2017Article
- PAR2-dependent activation of GSK3β regulates the survival of colon stem/progenitor cells.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- A highly potent agonist to protease-activated receptor-2 reveals apical activation of the airway epithelium resulting in Ca2+-regulated ion conductance.American journal of physiology. Cell physiology · 2014Article
- Minireview: More than just a hammer: ligand "bias" and pharmaceutical discovery.Molecular endocrinology (Baltimore, Md.) · 2014Review
- Extracellular nucleotides inhibit oxalate transport by human intestinal Caco-2-BBe cells through PKC-δ activation.American journal of physiology. Cell physiology · 2013Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Studies suggest that there are two distinct pools of proteinase-activated receptor-2 (PAR₂) present in intestinal epithelial cells: an apical pool accessible from the lumen, and a basolateral pool accessible from the interstitial space and blood. Although introduction of PAR₂ agonists such as 2-furoyl-LIGRL-O-NH₂ (2fAP) to the intestinal lumen can activate PAR₂, the presence of accessible apical PAR₂ has not been definitively shown. Furthermore, some studies have suggested that basolateral PAR₂ responses in the intestinal epithelium are mediated indirectly by neuropeptides released from enteric nerve fibers, rather than by intestinal PAR₂ itself. Here we identified accessible pools of both apical and basolateral PAR₂ in cultured Caco2-BBe monolayers and in mouse ileum. Activation of basolateral PAR₂ transiently increased short-circuit current by activating electrogenic Cl⁻ secretion, promoted dephosphorylation of the actin filament-severing protein, cofilin, and activated the transcription factor, AP-1, whereas apical PAR₂ did not. In contrast, both pools of PAR₂ activated extracellular signal-regulated kinase 1/2 (ERK1/2) via temporally and mechanistically distinct pathways. Apical PAR₂ promoted a rapid, biphasic PLCβ/Ca²(+)/PKC-dependent ERK1/2 activation, resulting in nuclear localization, whereas basolateral PAR₂ promoted delayed ERK1/2 activation which was predominantly restricted to the cytosol, involving both PLCβ/Ca²(+) and β-arrestin-dependent pathways. These results suggest that the outcome of PAR₂ activation is dependent on the specific receptor pool that is activated, allowing for fine-tuning of the physiological responses to different agonists.
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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.