ArticleNature communications2016
A phosphotyrosine switch regulates organic cation transporters.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 141 citations in OpenAlex.
- Pooled it
- Role of solute carrier transporters in the biodistribution and toxicity of chemotherapeutic drugs.Pharmacological reviews · 2026Review
- Insights and perspectives into the etiology of TKI-induced cardiotoxicity.ASPET discovery · 2026Article
- Drug-drug interactions in targeted cancer therapies: a focus on tyrosine kinase inhibitors.Expert review of clinical pharmacology · 2025Review
- Predicting OCT2/MATEs-Mediated Drug Interactions in Healthy Volunteers and Patients with Chronic Kidney Disease: Insights from Extended Clearance Concept, Endogenous Biomarkers, and In Vitro Inhibition Studies (Perspectives from the International Transporter Consortium).Clinical pharmacology and therapeutics · 2025Review
- Regulation of hepatic organic anion transporting polypeptide 1B-type transport function by the protein kinase LYN.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Genomic and Precision Medicine Approaches in Atherosclerotic Cardiovascular Disease: From Risk Prediction to Therapy-A Review.Biomedicines · 2025Review
- The "specific" P-glycoprotein inhibitor zosuquidar (LY335979) also weakly inhibits human organic cation transporters.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Coproporphyrin I as an in vitro fluorescent probe to measure OATP1B1 transport activity.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Resazurin dye is an in vivo sensor of kidney tubular function.Kidney international · 2025Article
- Bortezomib-induced peripheral neuropathy: from molecular mechanisms to clinical management.Frontiers in pharmacology · 2025Review
- Targeting YES1 Disrupts Mitotic Fidelity and Potentiates the Response to Taxanes in Triple-Negative Breast Cancer.Cancer research · 2024Article
- Pharmacometabolomics Approach to Explore Pharmacokinetic Variation and Clinical Characteristics of a Single Dose of Desvenlafaxine in Healthy Volunteers.Pharmaceutics · 2024Article
- Systematic Evaluation of Tyrosine Kinase Inhibitors as OATP1B1 Substrates Using a Competitive Counterflow Screen.Cancer research communications · 2024Article
- Interaction of the chemotherapeutic agent oxaliplatin and the tyrosine kinase inhibitor dasatinib with the organic cation transporter 2.Archives of toxicology · 2024Article
- Oligomerization of drug transporters: Forms, functions, and mechanisms.Acta pharmaceutica Sinica. B · 2024Review
- Impact of Drug-Mediated Inhibition of Intestinal Transporters on Nutrient and Endogenous Substrate Disposition…an Afterthought?Pharmaceutics · 2024Review
- Article
- Zinc finger protein 24-dependent transcription factor SOX9 up-regulation protects tubular epithelial cells during acute kidney injury.Kidney international · 2023Article
- The Role of Organic Cation Transporters in the Pharmacokinetics, Pharmacodynamics and Drug-Drug Interactions of Tyrosine Kinase Inhibitors.International journal of molecular sciences · 2023Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 11 institutions in 4 countries.
Funding
Abstract
Membrane transporters are key determinants of therapeutic outcomes. They regulate systemic and cellular drug levels influencing efficacy as well as toxicities. Here we report a unique phosphorylation-dependent interaction between drug transporters and tyrosine kinase inhibitors (TKIs), which has uncovered widespread phosphotyrosine-mediated regulation of drug transporters. We initially found that organic cation transporters (OCTs), uptake carriers of metformin and oxaliplatin, were inhibited by several clinically used TKIs. Mechanistic studies showed that these TKIs inhibit the Src family kinase Yes1, which was found to be essential for OCT2 tyrosine phosphorylation and function. Yes1 inhibition in vivo diminished OCT2 activity, significantly mitigating oxaliplatin-induced acute sensory neuropathy. Along with OCT2, other SLC-family drug transporters are potentially part of an extensive 'transporter-phosphoproteome' with unique susceptibility to TKIs. On the basis of these findings we propose that TKIs, an important and rapidly expanding class of therapeutics, can functionally modulate pharmacologically important proteins by inhibiting protein kinases essential for their post-translational regulation.
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What OpenQuestion holds
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.