2016 October

The topic of the month focuses on the regulation of hepatocyte transporters by protein kinase C. Hepatic transporters undergo post-translational regulations such as phosphorylation, dephosphorylation, translocation to and retrieval from cellular membranes and degradation by the ubiquitin-proteasome system. These post-translational regulations are mediated via several pathways such as cAMP, calcium, nitric oxide, phosphoinositide-3-kinase (PI3K), protein kinase C (PKC) and protein phosphatases.

Publications from network members

  • PLoS One. 2015;10:e0144667. Protein Kinase C-independent Inhibition of Organic Cation Transporter 1 activity by the bisindolylmaleimide Ro 31-8220. Mayati A, Bruyere A, Moreau A, Jouan E, Denizot C, Parmentier Y, Fardel O. PubMed
  • Biochem Pharmacol. 2015;98:703-17. Protein kinase C-dependent regulation of human hepatic drug transporter expression. Mayati A, Le Vee M, Moreau A, Jouan E, Bucher S, Stieger B, Denizot C, Parmentier Y, Fardel O. PKC regulation of hepatic transporters was studied in cultured cells. PubMed
  • Drug Metab Dispos. 2014;42:1964-70. Novel mechanism of impaired function of organic anion-transporting polypeptide 1B3 in human hepatocytes: post-translational regulation of OATP1B3 by protein kinase C activation. Powell J, Farasyn T, Köck K, Meng X, Pahwa S, Brouwer KL, Yue W. Post-translational regulation of OATP1B3 by protein kinase C activation was studied in human sandwich-cultured hepatocytes. PubMed
  • Pflugers Arch. 2014;466:77-89. Sodium-dependent bile salt transporters of the SLC10A transporter family: more than solute transporters. Anwer MS, Stieger B. PubMed
  • J Biol Chem. 2010;285:11336-47. Rapid modulation of the organic anion transporting polypeptide 2B1 (OATP2B1, SLCO2B1) function by protein kinase C-mediated internalization. Köck K, Koenen A, Giese B, Fraunholz M, May K, Siegmund W, Hammer E, Völker U, Jedlitschky G, Kroemer HK, Grube M. PubMed
  • Mol Pharmacol. 2007;71:1089-97. Function of both sinusoidal and canalicular transporters controls the concentration of organic anions within hepatocytes. Planchamp C, Hadengue A, Stieger B, Bourquin J, Vonlaufen A, Frossard JL, Quadri R, Becker CD, Pastor CM. In rat livers perfused with BOPTA, different experimental settings that modify concomitantly Oatp and Mrp2 activity through the PKC pathway change the hepatocyte concentrations of the contrast agent. PubMed

Publications from other research groups

  • J Biol Chem. 2015;290:24237-54. Regulation of plasma membrane localization of the Na+-taurocholate cotransporting polypeptide (Ntcp) by hyperosmolarity and tauroursodeoxycholate. Sommerfeld A, Mayer PG, Cantore M, Häussinger D. PubMed
  • J Hepatol. 2015;63:1440-8. Canalicular membrane MRP2/ABCC2 internalization is determined by Ezrin Thr567 phosphorylation in human obstructive cholestasis. Chai J, Cai SY, Liu X, Lian W, Chen S, Zhang L, Feng X, Cheng Y, He X, He Y, Chen L, Wang R, Wang H, Boyer JL, Chen W. PubMed
  • Biochim Biophys Acta. 2015;1848:2022-30. Protein kinase C affects the internalization and recycling of organic anion transporting polypeptide 1B1. Hong M, Hong W, Ni C2, Huang J, Zhou C. PubMed
  • Hepatology. 2014;60:1090-7. Role of protein kinase C isoforms in bile formation and cholestasis. Anwer MS. PubMed
  • Am J Physiol. 2013;305:G722-30. A dileucine motif is involved in plasma membrane expression and endocytosis of rat sodium taurocholate cotransporting polypeptide (Ntcp). Stross C, Kluge S, Weissenberger K, Winands E, Häussinger D, Kubitz R. PKC-mediated endocytosis regulates Ntcp membrane transporters. Endocytic retrieval protects hepatocytes from elevated bile salt concentrations and is of special interest, because NTCP has been identified as a receptor for the hepatitis B and D virus. PubMed
  • Hepatology. 2013;58:284-92. Taurolithocholate-induced MRP2 retrieval involves MARCKS phosphorylation by protein kinase Cϵ in HUH-NTCP Cells. Schonhoff CM, Webster CR, Anwer MS. PubMed
  • Biochim Biophys Acta. 2011;1812:1427-34. Interaction of Mrp2 with radixin causes reversible canalicular Mrp2 localization induced by intracellular redox status. Sekine S, Ito K, Saeki J, Horie T. PubMed
  • Br J Pharmacol. 2011;164:1547-57. Scoparone potentiates transactivation of the bile salt export pump gene and this effect is enhanced by cytochrome P450 metabolism but abolished by a PKC inhibitor. Yang D, Yang J, Shi D, Deng R, Yan B. PubMed
  • Am J Physiol. 2011;301:G60-8. Heterogeneous accumulation of fluorescent bile acids in primary rat hepatocytes does not correlate with their homogenous expression of ntcp. Murray JW, Thosani AJ, Wang P, Wolkoff AW. PubMed
  • Am J Physiol. 2010;299:G320-8. Protein kinase C induces endocytosis of the sodium taurocholate cotransporting polypeptide. Stross C, Helmer A, Weissenberger K, Görg B, Keitel V, Häussinger D, Kubitz R. PubMed
  • Pharmacol Ther. 2010;125:79-91. Pathophysiological regulation of renal SLC22A organic ion transporters in acute kidney injury: pharmacological and toxicological implications. Saito H. PubMed
  • Am J Physiol. 2009;297:G1259-67. PKC{epsilon}-dependent and -independent effects of taurolithocholate on PI3K/PKB pathway and taurocholate uptake in HuH-NTCP cell line. Schonhoff CM, Yamazaki A, Hohenester S, Webster CR, Bouscarel B, Anwer MS. PubMed