{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:34:34Z","timestamp":1792668874283,"version":"4.5.0"},"reference-count":55,"publisher":"American Society for Cell Biology (ASCB)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:p>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 TNF\u03b1, IFN\u03b3, 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.<\/jats:p>","DOI":"10.1091\/mbc.e18-08-0531","type":"journal-article","created":{"date-parts":[[2019,1,9]],"date-time":"2019-01-09T17:40:23Z","timestamp":1547055623000},"page":"566-578","source":"Crossref","is-referenced-by-count":48,"title":["Role of JAM-A tyrosine phosphorylation in epithelial barrier dysfunction during intestinal inflammation"],"prefix":"10.1091","volume":"30","author":[{"given":"Shuling","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Michigan, Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline M.","family":"Weight","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, University College London, London WC1E 6BT, United 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