Evidence map›Paper›PMID 19028678›Full record

ArticleThe Journal of biological chemistry2009

Activation of protein kinase Czeta increases OAT1 (SLC22A6)- and OAT3 (SLC22A8)-mediated transport.

Scott A Barros, Chutima Srimaroeng, Jennifer L Perry, Ramsey Walden, Neetu Dembla-Rajpal, Douglas H Sweet, John B Pritchard

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
1.5field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 49 citations in OpenAlex.

  1. Review
  2. Nutrition research and practice · 2024
    Article
  3. Review
  4. Renal Organic Anion Transporters 1 and 3 In Vitro: Gone but Not Forgotten.International journal of molecular sciences · 2023
    Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 1 country.

Scott A BarrosLaboratory of Pharmacology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709.
Chutima SrimaroengLaboratory of Pharmacology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709.
Jennifer L PerryLaboratory of Pharmacology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709.
Ramsey WaldenLaboratory of Pharmacology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709.
Neetu Dembla-RajpalLaboratory of Pharmacology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709.
Douglas H SweetDepartment of Pharmaceutical Sciences, Medical University of South Carolina, Charleston, South Carolina 29425.
John B PritchardLaboratory of Pharmacology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709. Electronic address: pritcha3@niehs.nih.gov.
Triangle · USMedical University of South Carolina · USNational Institute of Environmental Health Sciences · USNational Institutes of Health · US

Funding

ROLE OF ALTERED MEMBRANE FUNCTION IN XENOBIOTIC TOXICITYZ01ES080031 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI PRITCHARD, JOHN B · 1985 to 2008
$2.3M
Role Of Altered Membrane Function In Xenobiotic ToxicityZIAES080031 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI PRITCHARD, JOHN · 2009 to 2009
$524k
Intramural NIH HHS
6 · The paper itself

Abstract

Organic anion transporters (OATs) play a pivotal role in the clearance of small organic anions by the kidney, yet little is known about how their activity is regulated. A yeast two-hybrid assay was used to identify putative OAT3-associated proteins in the kidney. Atypical protein kinase Czeta (PKCzeta) was shown to bind to OAT3. Binding was confirmed in immunoprecipitation assays. The OAT3/PKCzeta interaction was investigated in rodent renal cortical slices from fasted animals. Insulin, an upstream activator of PKCzeta, increased both OAT3-mediated uptake of estrone sulfate (ES) and PKCzeta activity. Both effects were abolished by a PKCzeta-specific pseudosubstrate inhibitor. Increased ES transport was not observed in renal slices from OAT3-null mice. Transport of the shared OAT1/OAT3 substrate, rho-aminohippurate, behaved similarly, except that stimulation was reduced, not abolished, in the OAT3-null mice. This suggested that OAT1 activity was also modified by PKCzeta, subsequently confirmed using an OAT1-specific substrate, adefovir. Inhibition of PKCzeta also blocked the increase in ES uptake seen in response to epidermal growth factor and to activation of protein kinase A. Thus, PKCzeta acted downstream of the epidermal growth factor to protein kinase A signaling pathway. Activation of transport was accompanied by an increase in V(max) and was blocked by microtubule disruption, indicating that activation may result from trafficking of OAT3 into the plasma membrane. These data demonstrate that PKCzeta activation up-regulates OAT1 and OAT3 function, and that protein-protein interactions play a central role controlling these two important renal drug transporters.

Indexed as

AnimalsBiological TransportEnzyme ActivationIn Vitro TechniquesMiceMice, KnockoutOrganic Anion Transporters, Sodium-IndependentOrganic Anion Transport Protein 1Protein Kinase CProtein Kinase C zetaRatsRats, Sprague-DawleyOrganic Anion Transporters, Sodium-IndependentOrganic Anion Transport Protein 1organic anion transport protein 3Protein Kinase CProtein Kinase C zetaSlc22a6 protein, mouseSlc22a6 protein, rat

Identifiers

PMID19028678
PMCPMC2631969
OpenAlexW2150669385

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.