ArticleMolecular biology of the cell2019
Role of JAM-A tyrosine phosphorylation in epithelial barrier dysfunction during intestinal inflammation.
Article in Molecular biology of the cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- PathMED: an R toolkit for single-sample molecular scoring and machine learning with omics data.Bioinformatics (Oxford, England) · 2026Article
- Neonicotinoid pesticides disrupt gingival epithelial barrier function.Toxicology reports · 2026Article
- Food-derived molecules as regulators of intestinal tight junctions and barrier function: mechanisms and implications.Frontiers in drug delivery · 2026Review
- The Intestinal Barrier: A Multilayered Gatekeeper Against Systemic Disease.International journal of microbiology · 2026Review
- Antibacterial effects of epigallocatechin gallate against calf diarrhea-causingFrontiers in veterinary science · 2026Article
- Galactooligosaccharides Promote Gut Barrier Integrity and Exert Anti-Inflammatory Effects in DSS-Induced Colitis Through Microbiota Modulation.International journal of molecular sciences · 2025Article
- Article
- Ion transport and epithelial barrier dysfunction in experimental models of ulcerative colitis.American journal of physiology. Gastrointestinal and liver physiology · 2025Review
- The receptor protein tyrosine phosphatase PTPRK promotes intestinal repair and catalysis-independent tumour suppression.Journal of cell science · 2024Article
- RhoGDI1 regulates cell-cell junctions in polarized epithelial cells.Frontiers in cell and developmental biology · 2024Article
- Epithelial JAM-A is fundamental for intestinal wound repair in vivo.JCI insight · 2022Article
- Junctional adhesion molecule-A deletion increases phagocytosis and improves survival in a murine model of sepsis.JCI insight · 2022Article
- JAM-A signals through the Hippo pathway to regulate intestinal epithelial proliferation.iScience · 2022Article
- Perspectives on Vascular Regulation of Mechanisms Controlling Selective Immune Cell Function in the Tumor Immune Response.International journal of molecular sciences · 2022Review
- JAM-A interacts with α3β1 integrin and tetraspanins CD151 and CD9 to regulate collective cell migration of polarized epithelial cells.Cellular and molecular life sciences : CMLS · 2022Article
- Astrocytic junctional adhesion molecule-A regulates T-cell entry past the glia limitans to promote central nervous system autoimmune attack.Brain communications · 2022Article
- Junctional Adhesion Molecules: Potential Proteins in Atherosclerosis.Frontiers in cardiovascular medicine · 2022Review
- Mast Cell Specific Receptor Mrgprb2 Regulating Experimental Colitis is Associated with the Microbiota-Gut-Brain Axis.Journal of inflammation research · 2022Article
- Review
- Effect of F11R Gene Knockdown on Malignant Biological Behaviors of Pancreatic Cancer Cells.Journal of oncology · 2022Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Junctional adhesion molecule-A (JAM-A), an epithelial tight junction protein, plays an important role in regulating intestinal permeability through association with a scaffold signaling complex containing ZO-2, Afadin, and the small GTPase Rap2. Under inflammatory conditions, we report that the cytoplasmic tail of JAM-A is tyrosine phosphorylated (p-Y280) in association with loss of barrier function. While barely detectable Y280 phosphorylation was observed in confluent monolayers of human intestinal epithelial cells under basal conditions, exposure to cytokines TNFα, IFNγ, IL-22, or IL-17A, resulted in compromised barrier function in parallel with increased p-Y280. Phosphorylation was Src kinase dependent, and we identified Yes-1 and PTPN13 as a major kinase and phosphatase for p-JAM-A Y280, respectively. Moreover, cytokines IL-22 or IL-17A induced increased activity of Yes-1. Furthermore, the Src kinase inhibitor PP2 rescued cytokine-induced epithelial barrier defects and inhibited phosphorylation of JAM-A Y280 in vitro. Phosphorylation of JAM-A Y280 and increased permeability correlated with reduced JAM-A association with active Rap2. Finally, we observed increased phosphorylation of Y280 in colonic epithelium of individuals with ulcerative colitis and in mice with experimentally induced colitis. These findings support a novel mechanism by which tyrosine phosphorylation of JAM-A Y280 regulates epithelial barrier function during inflammation.
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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.