ArticlePharmaceutical research2004
Screening of the interaction between xenobiotic transporters and PDZ proteins.
Article in Pharmaceutical research, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 77 citations in OpenAlex.
- The Effect of Radixin on the Function and Expression of Organic Anion Transporting Polypeptide 1B1.Biology · 2025Article
- Oligomerization of drug transporters: Forms, functions, and mechanisms.Acta pharmaceutica Sinica. B · 2024Review
- Molecular Insights to the Structure-Interaction Relationships of Human Proton-Coupled Oligopeptide Transporters (PepTs).Pharmaceutics · 2023Review
- Interaction of Human OATP1B1 with PDZK1 Is Required for Its Trafficking to the Hepatocyte Plasma Membrane.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- Cloning and characterization of a novel functional organic anion transporting polypeptide 3A1 isoform highly expressed in the human brain and testis.Frontiers in pharmacology · 2022Article
- 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
- Effects of Osthol Isolated fromMolecules (Basel, Switzerland) · 2018Article
- Circadian clock component PERIOD2 regulates diurnal expression of NaScientific reports · 2018Article
- Trafficking and other regulatory mechanisms for organic anion transporting polypeptides and organic anion transporters that modulate cellular drug and xenobiotic influx and that are dysregulated in disease.British journal of pharmacology · 2017Review
- Analysis of the brain mural cell transcriptome.Scientific reports · 2016Article
- Dipeptide species regulate p38MAPK-Smad3 signalling to maintain chronic myelogenous leukaemia stem cells.Nature communications · 2015Article
- Drug Transporters and Na+/H+ Exchange Regulatory Factor PSD-95/Drosophila Discs Large/ZO-1 Proteins.Pharmacological reviews · 2015Review
- Transcriptional and functional regulation of the intestinal peptide transporter PEPT1.The Journal of physiology · 2014Review
- Organic anion-transporting polypeptides.Current topics in membranes · 2014Review
- Article
- OATPs, OATs and OCTs: the organic anion and cation transporters of the SLCO and SLC22A gene superfamilies.British journal of pharmacology · 2012Review
- Xenobiotic, bile acid, and cholesterol transporters: function and regulation.Pharmacological reviews · 2010Review
- Polyspecific organic cation transporters: structure, function, physiological roles, and biopharmaceutical implications.Pharmaceutical research · 2007Review
- Organic anion transporters of the SLC22 family: biopharmaceutical, physiological, and pathological roles.Pharmaceutical research · 2007Review
- Proton-coupled oligopeptide transporter family SLC15: physiological, pharmacological and pathological implications.Molecular aspects of medicineReview
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeXenobiotic transporters have been proposed to be involved in membrane penetration of various therapeutic agents. As little information is available on molecular mechanism of their functional regulation, we have attempted to clarify the protein-protein interactions of such transporters as a first step to identify their regulators.
methodsYeast two-hybrid screening was performed to examine the interaction between carboxylic terminus of various xenobiotic transporters and PDZ (PSD95, D1g and ZO1) domain-containing proteins. The interaction and functional regulation were also evaluated in pull-down, immunoprecipitation and transport studies.
resultsSpecific interaction with PDZ proteins was identified for several xenobiotic transporters including PEPT1, PEPT2, OCT3, OCTN1, OCTN2, OAT4, OATP-A, OATP-D, and OATP-F. The potent interaction was observed between PEPT2 and PDZK1, and deletion of the last four amino acids of the PEPT2 C-terminus almost completely abrogated such interaction. Recombinant PEPT2 C-terminus fusion protein can bind to purified His6-tagged PDZK1, confirming the involvement of two of four PDZ domains within PDZK1 in the interaction. Alanine-scanning mutation in PEPT2 revealed the presence of a consensus sequence (-T-X-L) that is responsible for the PDZK1 interaction. Transfection of PDZK1 increased the uptake of glycylsarcosine by PEPT2, whereas such stimulation was not observed for PEPT2 with the last four amino acids deleted.
conclusionsThese results first identified the interaction between PDZ proteins and the cytosolic tail of various xenobiotic transporters. PDZK1 directly interacts with PEPT2, exerting functional regulation of its transporting activity. The current findings imply the localization of PEPT2 within a protein network constructed from PDZK1 and other transporter proteins.
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