ArticleAmerican journal of physiology. Cell physiology2012
Molecular mechanism of interleukin-2-induced mucosal homeostasis.
Article in American journal of physiology. Cell physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- Kindlin-3 sustains cytokine interleukin-2 signaling by linking its receptor to integrin LFA-1.The Journal of biological chemistry · 2026Article
- Mucosal implications of oral Jak3-targeted drugs in COVID patients.Molecular medicine (Cambridge, Mass.) · 2025Review
- The Potential Role of Vitamin E and the Mechanism in the Prevention and Treatment of Inflammatory Bowel Disease.Foods (Basel, Switzerland) · 2024Review
- Conditional deletion of CD25 in the corneal epithelium reveals sex differences in barrier disruption.The ocular surface · 2023Article
- Article
- JAK3 Is Expressed in the Nucleus of Malignant T Cells in Cutaneous T Cell Lymphoma (CTCL).Cancers · 2021Article
- Mucosal Epithelial Jak Kinases in Health and Diseases.Mediators of inflammation · 2021Review
- The Impact of a New Interleukin-2-Based Immunotherapy Candidate on Urothelial Cells to Support Use for Intravesical Drug Delivery.Life (Basel, Switzerland) · 2020Article
- JANEX-1 improves acute pulmonary embolism through VEGF and FAK in pulmonary artery smooth muscle cells.Experimental biology and medicine (Maywood, N.J.) · 2020Article
- JAK-STAT pathway targeting for the treatment of inflammatory bowel disease.Nature reviews. Gastroenterology & hepatology · 2020Review
- Low-dose interleukin-2 alleviates dextran sodium sulfate-induced colitis in mice by recovering intestinal integrity and inhibiting AKT-dependent pathways.Theranostics · 2020Article
- Intestinal breast cancer resistance protein (BCRP) requires Janus kinase 3 activity for drug efflux and barrier functions in obesity.The Journal of biological chemistry · 2019Article
- Review
- Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2019Article
- Janus kinase 3 regulates adherens junctions and epithelial mesenchymal transition through β-catenin.The Journal of biological chemistry · 2017Article
- Janus Kinase 3, a Novel Regulator for Smooth Muscle Proliferation and Vascular Remodeling.Arteriosclerosis, thrombosis, and vascular biology · 2017Article
- Chicken-Specific Kinome Array Reveals that Salmonella enterica Serovar Enteritidis Modulates Host Immune Signaling Pathways in the Cecum to Establish a Persistence Infection.International journal of molecular sciences · 2016Article
- Role of Janus Kinase 3 in Predisposition to Obesity-associated Metabolic Syndrome.The Journal of biological chemistry · 2015Article
- Adapter protein Shc regulates Janus kinase 3 phosphorylation.The Journal of biological chemistry · 2014Article
- Immune-epithelial crosstalk at the intestinal surface.Journal of gastroenterology · 2014Review
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Sustained damage to the mucosal lining in patients with inflammatory bowel disease (IBD) facilitates translocation of intestinal microbes to submucosal immune cells leading to chronic inflammation. Previously, we demonstrated the role of Jak3 in IL-2-induced intestinal epithelial cell (IEC) migration, one of the early events during intestinal wound repair. In this study, we demonstrate that IL-2 also plays a role in IEC homeostasis through concentration-dependent regulation of IEC proliferation and cell death. At lower concentrations (≤50 U/ml), IL-2 promoted proliferation, while at higher concentrations (100 U/ml), it promoted apoptosis. Activation by IL-2 led to tyrosine phosphorylation-dependent interactions between Jak3 and p52ShcA only at lower concentrations. Phosphatase SHP1 dephosphorylated IL-2-induced phosphorylated p52ShcA. Higher concentrations of IL-2 decreased the phosphorylation of Jak3 and p52ShcA, disrupted their interactions, redistributed Jak3 to the nucleus, and induced apoptosis in IEC. IL-2 also induced dose-dependent upregulation of p52shcA and downregulation of jak3-mRNA. Constitutive overexpression and mir-shRNA-mediated knockdown studies showed that expression of both Jak3 and p52ShcA were necessary for IL-2-induced proliferation of IEC. Doxycycline-regulated sh-RNA expression demonstrated that IL-2-induced downregulation of jak3-mRNA was responsible for higher IL-2-induced apoptosis in IEC. Collectively, these data demonstrate a novel mechanism of IL-2-induced mucosal homeostasis through posttranslational and transcriptional regulation of Jak3 and p52ShcA.
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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.