Novel mechanism of impaired function of organic anion-transporting polypeptide 1B3 in human hepatocytes: post-translational regulation of OATP1B3 by protein kinase C activation.

@article{Powell2014NovelMO,
  title={Novel mechanism of impaired function of organic anion-transporting polypeptide 1B3 in human hepatocytes: post-translational regulation of OATP1B3 by protein kinase C activation.},
  author={John Powell and Taleah Farasyn and Kathleen Koeck and Xiaojie Meng and Sonia Pahwa and Kim L R Brouwer and Wei Yue},
  journal={Drug metabolism and disposition: the biological fate of chemicals},
  year={2014},
  volume={42 11},
  pages={1964-70}
}
The organic anion-transporting polypeptide (OATP) 1B3 is a membrane transport protein that mediates hepatic uptake of many drugs and endogenous compounds. Currently, determination of OATP-mediated drug-drug interactions in vitro is focused primarily on direct substrate inhibition. Indirect inhibition of OATP1B3 activity is under-appreciated. OATP1B3 has putative protein kinase C (PKC) phosphorylation sites. Studies were designed to determine the effect of PKC activation on OATP1B3-mediated… CONTINUE READING

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Carrier ProteinsIs biochemical function of gene productOrganic Anion Transport Polypeptides
The organic anion - transporting polypeptide ( OATP ) 1B3 is a membrane transport protein that mediates hepatic uptake of many drugs and endogenous compounds .
To determine the mechanism(s ) underlying the indirect inhibition of OATP1B3 activity upon PKC activation , adenoviral vectors expressing FLAG - Myc - tagged OATP1B3 ( Ad - OATP1B3 ) were transduced into human hepatocytes ; surface expression and phosphorylation of OATP1B3 were determined by biotinylation and by an anti - phosphor - Ser / Thr / Tyr antibody , respectively .
To determine the mechanism(s ) underlying the indirect inhibition of OATP1B3 activity upon PKC activation , adenoviral vectors expressing FLAG - Myc - tagged OATP1B3 ( Ad - OATP1B3 ) were transduced into human hepatocytes ; surface expression and phosphorylation of OATP1B3 were determined by biotinylation and by an anti - phosphor - Ser / Thr / Tyr antibody , respectively .
Organic Anion Transport PolypeptidesGene product plays role in biological processTransmembrane Transport
The organic anion - transporting polypeptide ( OATP ) 1B3 is a membrane transport protein that mediates hepatic uptake of many drugs and endogenous compounds .
To determine the mechanism(s ) underlying the indirect inhibition of OATP1B3 activity upon PKC activation , adenoviral vectors expressing FLAG - Myc - tagged OATP1B3 ( Ad - OATP1B3 ) were transduced into human hepatocytes ; surface expression and phosphorylation of OATP1B3 were determined by biotinylation and by an anti - phosphor - Ser / Thr / Tyr antibody , respectively .
To determine the mechanism(s ) underlying the indirect inhibition of OATP1B3 activity upon PKC activation , adenoviral vectors expressing FLAG - Myc - tagged OATP1B3 ( Ad - OATP1B3 ) were transduced into human hepatocytes ; surface expression and phosphorylation of OATP1B3 were determined by biotinylation and by an anti - phosphor - Ser / Thr / Tyr antibody , respectively .
To determine the mechanism(s ) underlying the indirect inhibition of OATP1B3 activity upon PKC activation , adenoviral vectors expressing FLAG - Myc - tagged OATP1B3 ( Ad - OATP1B3 ) were transduced into human hepatocytes ; surface expression and phosphorylation of OATP1B3 were determined by biotinylation and by an anti - phosphor - Ser / Thr / Tyr antibody , respectively .
To determine the mechanism(s ) underlying the indirect inhibition of OATP1B3 activity upon PKC activation , adenoviral vectors expressing FLAG - Myc - tagged OATP1B3 ( Ad - OATP1B3 ) were transduced into human hepatocytes ; surface expression and phosphorylation of OATP1B3 were determined by biotinylation and by an anti - phosphor - Ser / Thr / Tyr antibody , respectively .
PMA pretreatment markedly increased OATP1B3 phosphorylation without affecting surface or total OATP1B3 protein levels .
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