ArticlePharmaceutical research2010
Regulation of human organic anion transporter 4 by protein kinase C and NHERF-1: altering the endocytosis of the transporter.
Article in Pharmaceutical research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Is It Time to Use Modeling of Cellular Transporter Homeostasis to Inform Drug-Drug Interaction Studies: Theoretical Considerations.The AAPS journal · 2021Article
- Post-translational regulation of the major drug transporters in the families of organic anion transporters and organic anion-transporting polypeptides.The Journal of biological chemistry · 2020Review
- Uraemic syndrome of chronic kidney disease: altered remote sensing and signalling.Nature reviews. Nephrology · 2019Review
- Activation of Protein Kinase A Stimulates SUMOylation, Expression, and Transport Activity of Organic Anion Transporter 3.The AAPS journal · 2019Article
- The mechanistic links between insulin and human organic anion transporter 4.International journal of pharmaceutics · 2019Article
- Posttranslational Regulation of Organic Anion Transporters by Ubiquitination: Known and Novel.Medicinal research reviews · 2016Review
- Drug Transporters and Na+/H+ Exchange Regulatory Factor PSD-95/Drosophila Discs Large/ZO-1 Proteins.Pharmacological reviews · 2015Review
- Novel mechanism of impaired function of organic anion-transporting polypeptide 1B3 in human hepatocytes: post-translational regulation of OATP1B3 by protein kinase C activation.Drug metabolism and disposition: the biological fate of chemicals · 2014Article
- Article
- Regulation of human organic anion transporter 4 by parathyroid hormone-related protein and protein kinase A.International journal of biochemistry and molecular biology · 2012Article
- Protein kinase C regulates the internalization and function of the human organic anion transporting polypeptide 1A2.British journal of pharmacology · 2011Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
purposeHuman organic anion transporter 4 (hOAT4) belongs to a family of organic anion transporters that play critical roles in the body disposition of clinically important drugs. We have previously shown that the activity of hOAT4 was down-regulated by activation of PKC and up-regulated by PDZ protein NHERF-1. Here, we investigated the mechanisms underlying such regulations.
methodsCOS-7 cells expressing hOAT4 were treated with PKC activator phorbol 12-myristate 13-acetate (PMA) or transfected with dominant negative mutants of dynamin-2 or Eps15 or transfected with NHERF-1. The internalization and the function of hOAT4 were then determined.
resultsWe showed that hOAT4 constitutively internalized from and recycled back to plasma membrane. Transfection of dominant negative mutants of dynamin-2 or Eps15 into the cells, all of which block clathrin-dependent endocytotic pathway, significantly blocked hOAT4 internalization. Treatment of cells with PMA accelerated hOAT4 internalization, whereas transfection of cells with NHERF-1 attenuated hOAT4 internalization.
conclusionOur studies demonstrated that i) hOAT4 undergoes constitutive trafficking between cell surface and intracellular compartments, ii) hOAT4 internalization partly occurs through clathrin-dependent pathway, iii) the down-regulation of hOAT4 activity by activation of PKC and the up-regulation of hOAT4 activity by NHERF-1 are mediated through alteration of hOAT4 internalization.
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