ArticleJournal of pharmacological sciences2018
AG490, a JAK2-specific inhibitor, downregulates the expression and activity of organic anion transporter-3.
Article in Journal of pharmacological sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 32 citations in OpenAlex.
- Recent Advances on the Regulations of Organic Anion Transporters.Pharmaceutics · 2024Review
- CAFs-derived rho-associated kinase1 mediated EMT to promote laryngeal squamous cell carcinoma metastasis.Cancer cell international · 2023Article
- Inhibition of proteasome, but not lysosome, upregulates organic anion transporter 3 in vitro and in vivo.Biochemical pharmacology · 2023Article
- NEDD4L in human tumors: regulatory mechanisms and dual effects on anti-tumor and pro-tumor.Frontiers in pharmacology · 2023Review
- Cyanidin-3-O-glucoside plays a protective role against renal ischemia/ reperfusion injury via the JAK/STAT pathway.Acta cirurgica brasileira · 2023Article
- Roles of STAT3 in the pathogenesis and treatment of glioblastoma.Frontiers in cell and developmental biology · 2023Review
- The expression and the tumor suppressor role of CLDN6 in colon cancer.Molecular and cellular biochemistry · 2022Article
- Review
- Oral Proteasomal Inhibitors Ixazomib, Oprozomib, and Delanzomib Upregulate the Function of Organic Anion Transporter 3 (OAT3): Implications in OAT3-Mediated Drug-Drug Interactions.Pharmaceutics · 2021Article
- Regulation of organic anion transporters: Role in physiology, pathophysiology, and drug elimination.Pharmacology & therapeutics · 2021Review
- Insights Into the Biological Role of NEDD4L E3 Ubiquitin Ligase in Human Cancers.Frontiers in oncology · 2021Review
- CCL18-NIR1 promotes oral cancer cell growth and metastasis by activating the JAK2/STAT3 signaling pathway.BMC cancer · 2020Article
- Insulin-like growth factor 1 modulates the phosphorylation, expression, and activity of organic anion transporter 3 through protein kinase A signaling pathway.Acta pharmaceutica Sinica. B · 2020Article
- The mechanistic links between insulin and human organic anion transporter 4.International journal of pharmaceutics · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Human organic anion transporter-3 (hOAT3) is richly expressed in the kidney, where it plays critical roles in the secretion of clinically important drugs, including anti-viral therapeutics, anti-cancer drugs, antibiotics, antihypertensives, and anti-inflammatories. In the current study, we examined the role of AG490, a specific inhibitor of the Janus tyrosine kinase 2 (JAK2), in hOAT3 transport activity in the kidney COS-7 cells. AG490 induced a time- and concentration-dependent inhibition of hOAT3-mediated uptake of estrone sulfate, a prototypical substrate for the transporter. The inhibitory effect of AG490 correlated with a reduced expression of hOAT3 at the cell surface. Our lab previously demonstrated that Nedd4-2, a ubiquitin ligase, down regulates OAT expression and transport activity by enhancing OAT ubiquitination, which leads to an internalization of OAT from cell surface to intracellular compartments and subsequent degradation. In the current study, we showed that treatment of hOAT3-expressing cells with AG490 resulted in an enhanced hOAT3 ubiquitination and degradation, which was accompanied by a strengthened association of Nedd4-2 with hOAT3 and a reduction in Nedd4-2 phosphorylation. SiRNA knockdown of endogenous Nedd4-2 abrogated the effects of AG490 on hOAT3. In summary, our study demonstrated that AG490 regulates hOAT3 expression and transport activity through the modulation of Nedd4-2.
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