ArticleThe Journal of biological chemistry2019
Intestinal breast cancer resistance protein (BCRP) requires Janus kinase 3 activity for drug efflux and barrier functions in obesity.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- NEK2 drives pathogenesis, drug resistance, and LMP1 expression in EBV-positive non-Hodgkin lymphoma.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- Gut Microbiota in the Regulation of Intestinal Drug Transporters: Molecular Mechanisms and Pharmacokinetic Implications.International journal of molecular sciences · 2025Review
- Mucosal implications of oral Jak3-targeted drugs in COVID patients.Molecular medicine (Cambridge, Mass.) · 2025Review
- Beyond ADME: The Endogenous Functions of Drug Transporters and Its Impact on Human Disease.Pharmaceutics · 2025Review
- Drug-Induced Liver Injury Associated With Emerging Cancer Therapies.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Expression, Function, and Regulation of ABCG2 on the Intestinal Epithelial Barrier Permeability.Current drug metabolism · 2025Review
- Oligomerization of drug transporters: Forms, functions, and mechanisms.Acta pharmaceutica Sinica. B · 2024Review
- Regulation of ABC transporters by sex steroids may explain differences in drug resistance between sexes.Journal of physiology and biochemistry · 2023Review
- Effects of bacterial and viral pathogen-associated molecular patterns (PAMPs) on multidrug resistance (MDR) transporters in brain endothelial cells of the developing human blood-brain barrier.Fluids and barriers of the CNS · 2023Article
- Article
- Regulation of Drug Transport Proteins-From Mechanisms to Clinical Impact: A White Paper on Behalf of the International Transporter Consortium.Clinical pharmacology and therapeutics · 2022Review
- Managing Cancer Drug Resistance from the Perspective of Inflammation.Journal of oncology · 2022Review
- Inulin supplementation ameliorates hyperuricemia and modulates gut microbiota in Uox-knockout mice.European journal of nutrition · 2021Article
- Mucosal Epithelial Jak Kinases in Health and Diseases.Mediators of inflammation · 2021Review
- Iron Metabolism in Obesity and Metabolic Syndrome.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Breast cancer resistance protein (BCRP) is a member of ATP-binding cassette (ABC) transporter proteins whose primary function is to efflux substrates bound to the plasma membrane. Impaired intestinal barrier functions play a major role in chronic low-grade inflammation (CLGI)-associated obesity, but the regulation of BCRP during obesity and its role in maintaining the intestinal barrier function during CLGI-associated obesity are unknown. In the present study, using several approaches, including efflux assays, immunoprecipitation, immunoblotting, immunohistochemistry, paracellular permeability assay, FACS, cytokine assay, and immunofluorescence microscopy, we report that obese individuals have compromised intestinal BCRP functions and that diet-induced obese mice recapitulate these outcomes. We demonstrate that the compromised BCRP functions during obesity are because of loss of Janus kinase 3 (JAK3)-mediated tyrosine phosphorylation of BCRP. Our results indicate that JAK3-mediated phosphorylation of BCRP promotes its interactions with membrane-localized β-catenin essential not only for BCRP expression and surface localization, but also for the maintenance of BCRP-mediated intestinal drug efflux and barrier functions. We observed that reduced intestinal JAK3 expression during human obesity or JAK3 knockout in mouse or siRNA-mediated β-catenin knockdown in human intestinal epithelial cells all result in significant loss of intestinal BCRP expression and compromised colonic drug efflux and barrier functions. Our results uncover a mechanism of BCRP-mediated intestinal drug efflux and barrier functions and establish a role for BCRP in preventing CLGI-associated obesity both in humans and in mice.
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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.