Cellular Regulation of Hepatic Bile Acid Transport in Health and Cholestasis

Hepatology

Volumn 39, Issue 3, 2004, Pages 581-590

  Anwer, M Sawkat ^a  

^a TUFTS UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BILE ACID; CALCIUM; CELL NUCLEUS RECEPTOR; CYCLIC AMP; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHOPROTEIN PHOSPHATASE; PROTEIN KINASE C; STAT PROTEIN;

BILE ACID METABOLISM; BILE ACID SYNTHESIS; BILIARY EXCRETION; CHOLESTASIS; ENDOPLASMIC RETICULUM; INTRAHEPATIC BILE DUCT; LIVER CELL; LIVER METABOLISM; PATHOGENESIS; PRIORITY JOURNAL; RECEPTOR AFFINITY; SHORT SURVEY; SIGNAL TRANSDUCTION; TRANSCRIPTION REGULATION; TRANSPORT KINETICS;

ANIMALS; BILE ACIDS AND SALTS; BIOLOGICAL TRANSPORT; CHOLESTASIS; HEALTH; HUMANS; LIVER;

EID: 1542724881     PISSN: 02709139     EISSN: None     Source Type: Journal    
DOI: 10.1002/hep.20090     Document Type: Short Survey

References (116)

1. Anwer MS. Transhepatic solute transport and bile formation. Adv Vet Sci Comp Med 1993;37:1-29.
2. Anwer MS. Cellular and molecular biology of the liver. Curr Opin Gastroenterol 1998;14:182-190.
3. Trauner M, Boyer JL. Bile salt transporters: molecular characterization, function, and regulation. Physiol Rev 2003;83:633-671.
4. Kanno N, Lesage G, Glaser S, Alpini G. Regulation of cholangiocyte bicarbonate secretion. Am J Physiol Gastrointest Liver Physiol 2001;281:G612-G625.
5. Mennone A, Biemesderfer D, Negoianu D, Yang CL, Abbiati T, Schultheis PJ, Shull GE, et al. Role of sodium/hydrogen exchanger isoform NHE3 in fluid secretion and absorption in mouse and rat cholangiocytes. Am J Physiol Gastrointest Liver Physiol 2001;280:G247-G254.
6. Hagenbuch B, Meier PJ. The superfamily of organic anion transporting polypeptides. Biochim Biophys Acta 2003;1609:1-18.
7. Singh SK, Mennone A, Gigliozzi A, Fraioli F, Boyer JL. Cl(-)-dependent secretory mechanisms in isolated rat bile duct epithelial units. Am J Physiol Gastrointest Liver Physiol 2001;281:G438-G446.
8. Bohan A, Boyer JL. Mechanisms of hepatic transport of drugs: implications for cholestatic drug reactions. Semin Liver Dis 2002;22:123-136.
9. Elferink RO, Groen AK. Genetic defects in hepatobiliary transport. Biochim Biophys Acta 2002;1586:129-145.
10. Lee J, Boyer JL. Molecular alterations in hepatocyte transport mechanisms in acquired cholestatic liver disorders. Semin Liver Dis 2000;20:373-384.
11. Jansen PL, Muller M, Sturm E. Genes and cholestasis. HEPATOLOGY 2001;34:1067-1074.
12. Lee JM, Stieger B, Soroka CJ, Stieger B, Meier PJ, Boyer JL. Expression of the bile salt export pump is maintained after chronic cholestasis in the rat. Gastroenterology 2000;118:163-172.
13. Trauner M, Arrese M, Soroka CJ, Ananthanarayanan M, Koeppel TA, Schlosser SF, Suchy J, et al. The rat canalicular conjugate export pump (Mrp2) is down-regulated in intrahepatic and obstructive cholestasis. Gastroenterology 1997;113:255-264.
14. Soroka CJ, Lee JM, Azzaroli F, Boyer JL. Cellular localization and up-regulation of multidrug resistance-associated protein 3 in hepatocytes and cholangiocytes during obstructive cholestasis in rat liver. HEPATOLOGY 2001;33:783-791.
15. Donner MG, Keppler D. Up-regulation of basolateral multidrug resistance protein 3 (Mrp3) in cholestatic rat liver. HEPATOLOGY 2001;34:351-359.
16. Paulusma CC, Kool M, Bosma PJ, Scheffer GL, ter Borg F, Scheper RJ, Tytgat GN, et al. A mutation in the human canalicular multispecific organic anion transporter gene causes the Dubin-Johnson syndrome. HEPATOLOGY 1997;25:1539-1542.
17. Strautnieks SS, Bull LN, Knisely AS, Kocoshis SA, Dahl N, Arnell H, Sokal E, et al. A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis. Nat Genet 1998;20:233-238.
18. De Vree JM, Jacquemin E, Sturm E, Cresteil D, Bosma PJ, Aten J, Deleuze JF, et al. Mutations in the MDR3 gene cause progressive familial intrahepatic cholestasis. Proc Natl Acad Sci USA 1998;95:282-287.
19. Wang L, Soroka CJ, Boyer JL. The role of bile salt export pump mutations in progressive familial intrahepatic cholestasis type II. J Clin Invest 2002;110:965-972.
20. Chiang JY. Bile acid regulation of hepatic physiology: III. Bile acids and nuclear receptors. Am J Physiol Gastrointest Liver Physiol 2003;284:G349-G356.
21. Karpen SJ. Nuclear receptor regulation of hepatic function. J Hepatol 2002;36:832-850.
22. Meier PJ, Stieger B. Molecular mechanisms in bile formation. News Physiol Sci 2000;15:89-93.
23. Bouscarel B, Kroll SD, Fromm H. Signal transduction and hepatocellular bile acid transport: cross talk between bile acids and second messengers. Gastroenterology 1999;117:433-452.
24. Kullak-Ublick GA, Beuers U, Paumgartner G. Hepatobiliary transport. J Hepatol 2000;32(1 Suppl):3-18.
25. Oswald M, Kullak-Ublick GA, Paumgartner G, Beuers U. Expression of hepatic transporters OATP-C and MRP2 in primary sclerosing cholangitis. Liver 2001;21:247-253.
26. Zollner G, Fickert P, Zenz R, Fuchsbichler A, Stumptner C, Kenner L, Ferenci P, et al. Hepatobiliary transporter expression in percutaneous liver biopsies of patients with cholestatic liver diseases. HEPATOLOGY 2001;33:633-646.
27. Jung D, Kullak-Ublick GA. Hepatocyte nuclear factor 1 alpha: a key mediator of the effect of bile acids on gene expression. HEPATOLOGY 2003;37:622-631.
28. Arrese M, Trauner M, Ananthanarayanan M, Pizarro M, Solis N, Accatino L, Soroca C, et al. Down-regulation of the Na+/taurocholate cotransporting polypeptide during pregnancy in the rat. J Hepatol 2003;38:148-155.
29. Trauner M, Arrese M, Lee H, Boyer JL, Karpen SJ. Endotoxin down-regulates rat hepatic ntcp gene expression via decreased activity of critical transcription factors. J Clin Invest 1998;101:2092-2100.
30. Ananthanarayanan M, Balasubramanian N, Makishima M, Mangelsdorf DJ, Suchy FJ. Human bile salt export pump promoter is transactivated by the farnesoid X receptor/bile acid receptor. J Biol Chem 2001;276:28857-28865.
31. Wolters H, Elzinga BM, Ballet JF, Boverhof R, Schwarz M, Stieger B, Verkade HJ, et al. Effects of bile salt flux variations on the expression of hepatic bile salt transporters in vivo in mice. J Hepatol 2002;37:556-563.
32. Nowicki MJ, Shneider BL, Paul JM, Heubi JE. Gluococorticoids upregulate taurocholate transport by ileal bursh-border membrane. Am J Physiol 1997;273:G197-G203.
33. Ganguly TC, O'Brien ML, Karpen SJ, Suchy FJ, Vote M. Regulation of the rat liver sodium-dependent bile acid cotransporter gene by prolactin. Mediation of transcriptional activation by Stat5. J Clin Invest 1997;99:2906-2914.
34. Hayakawa T, Bruck R, Ng OC, Boyer JL. DBcAMP stimulates vesicle transport and HRP excretion in isolated perfused rat liver. Am J Physiol 1990;259:G727-G735.
35. Benedetti A, Strazzabosco M, Ng OC, Boyer JL. Regulation of activity and apical targeting of the Cl-/HCO3-exchanger in rat hepatocytes. Proc Natl Acad Sci USA 1994;91:792-796.
36. Grüne S, Engelking LR, Anwer MS. Role of intracellular calcium and protein kinases in the activation of hepatic Na+/taurocholate cotransport by cyclic AMP. J Biol Chem 1993;268:17734-17741.
37. Myers NC, Grüne S, Jameson HL, Anwer MS. cGMP stimulates bile acid-independent bile formation and biliary bicarbonate excretion. Am J Physiol 1996;270:G418-G424.
38. +-taurocholate cotransport by translocating transporter to plasma membranes. Am J Physiol 1997;273:G842-G848.
39. Dranoff JA, McClure M, Burgstahler AD, Denson LA, Crawford AR, Crawford JM, Karpen SJ, et al. Short-term regulation of bile acid uptake by microfilament-dependent translocation of ntcp to the plasma membrane. HEPATOLOGY 1999;30:223-229.
40. Roelofsen H, Soroka CJ, Keppler D, Boyer JL. Cyclic AMP stimulates sorting of the canalicular organic anion transporter (Mrp2/cMoat) to the apical domain in hepatocyte couplets. J Cell Sci 1998;111:1137-1145.
41. Gatmaitan ZC, Nies AT, Arias IM. Regulation and translocation of ATP-dependent apical membrane proteins in rat liver. Am J Physiol 1997;272:G1041-G1049.
42. Kipp H, Pichetshote N, Arias IM. Transporters on demand: intrahepatic pools of canalicular ATP binding cassette transporters in rat liver. J Biol Chem 2001;276:7218-7224.
43. Boyer JL, Soroka CJ. Vesicle targeting to the apical domain regulates bile excretory function in isolated rat hepatocyte couplets. Gastroenterology 1995;109:1600-1611.
44. Webster CRL, Anwer MS. Role of the PI3K/PKB signaling pathway in cAMP-mediated translocation of rat liver Ntcp. Am J Physiol 1999; 277:G1165-G1172.
45. Misra S, Varticovski L, Arias IM. Mechanisms by which cAMP increases bile acid secretion in rat liver and canalicular membrane vesicles. Am J Physiol Gastrointest Liver Physiol 2003;285:G316-G324.
46. Mei FC, Qiao J, Tsygankova OM, Meinkoth JL, Quilliam LA, Cheng X. Differential signaling of cyclic AMP: opposing effects of exchange protein directly activated by cyclic AMP and cAMP-dependent protein kinase on protein kinase B activation. J Biol Chem 2002;277:11497-11504.
47. Kawasaki H, Springett GM, Mochizuki N, Toki S, Nakaya M, Matsuda M, et al. A family of cAMP-binding proteins that directly activate Rap 1. Science 1998;282:2275-2279.
48. Davidson HW, McGowan CH, Balch WE. Evidence for the regulation of exocytic transport by protein phosphorylation. J Cell Biol 1992;116:1343-1355.
49. Exton JH. Role of phosphoinositides in the regulation of liver-function. HEPATOLOGY 1988;8:152-166.
50. Joseph SK, Ryan SV. Phosphorylation of the inositol trisphosphate receptor in isolated rat hepatocytes. J Biol Chem 1993;268:23059-23065.
51. + mobilization without increasing the cellular levels of inositol polyphosphates. J Biol Chem 1991;266:4772-4781.
52. Matsuzaki Y, Bouscarel B, Le M, Ceryak S, Gettys TW, Shoda J, Fromm H, et al. Effect of cholestasis on regulation of cAMP synthesis by glucagon and bile acids in isolated hepatocytes. Am J Physiol 1997;273:G164-G174.
53. Bouscarel B, Matsuzaki Y, Le M, Gettys TW, Fromm H. Changes in G protein expression account for impaired modulation of hepatic cAMP formation after BDL. Am J Physiol 1998;274:G1151-G1159.
54. Crocenzi FA, Mottino AD, Cao J, Veggi LM, Pozzi EJ, Vore M, Coleman R, et al. Estradiol-17beta-D-glucuronide induces endocytic internalization of Bsep in rats. Am J Physiol Gastrointest Liver Physiol 2003;285:G449-G459.
55. Crocenzi FA, Mottino AD, Sanchez Pozzi EJ, Pellegrino JM, Rodriguez Garay EA, Milkiewicz P, Vote M, et al. Impaired localisation and transport function of canalicular Bsep in taurolithocholate induced cholestasis in the rat. Gut 2003;52:1170-1177.
56. Hirohashi T, Suzuki H, Takikawa H, Sugiyama Y. ATP-dependent transport of bile salts by rat multidrug resistance-associated protein 3 (Mrp3). J Biol Chem 2000;275:2905-2910.
57. ++ in hepatic bile formation and taurocholate transport. Am J Physiol 1985;249:G711-G718.
58. Reichen J, Berr F, Le M, Warren GH. Characterization of calcium deprivation-induced cholestasis in the perfused rat liver. Am J Physiol 1985;249:G48-G57.
59. 2+-mobilizing agents. Am J Physiol 1996;271:G1084-G1095.
60. Kuhn WF, Gewirtz DA. Stimulation of taurocholate and glycocholate efflux from the rat hepatocyte by arginine vasopressin. Am J Physiol 1988;254:G732-G740.
61. Kuhn WF, Heuman DM, Vlahcevic ZR, Gewirtz DA. Receptor-mediated stimulation of taurocholate efflux from the rat hepatocyte and the ex vivo perfused rat liver. Eur J Pharmacol 1990;175:117-128.
62. Lukas TJ, Haiech J, Lau W, Craig TA, Zimmer WE, Shattuck RL, Shoemaker MO, et al. Calmodulin and calmodulin-regulated protein kinases as transducers of intracellular calcium signals. Cold Spring Harb Symp Quant Biol 1988;53:185-193.
63. + exchanger by arginine vasopressin in hepatocytes. HEPATOLOGY 1994;20:1309-1317.
64. Mukhopadhayay S, Ananthanarayanan M, Stieger B, Meier PJ, Suchy FJ, Anwer MS. Sodium taurocholate cotransporting polypeptide is a serine, threonine phosphoprotein and is dephosphorylated by cyclic AMP. HEPATOLOGY 1998;28:1629-1636.
65. Webster CRL, Blanch C, Anwer MS. Role of PP2B in cAMP-induced dephosphorylation and translocation of NTCP. Am J Physiol Gastrointest Liver Physiol 2002;283:G44-G50.
66. ++ activity of isolated rat hepatocytes. HEPATOLOGY 1988;8:887-891.
67. Beuers U, Nathanson MH, Boyer JL. Effects of tauroursodeoxycholic acid on cytosolic Ca2+ signals in isolated rat hepatocytes. Gastroenterology 1993;104:604-612.
68. Scholmerich J, Baumgartner U, Miyai K, Gerok W. Tauroursodeoxycholate prevents taurolithocholate-induced cholestasis and toxicity in rat liver. J Hepatol 1990;10:280-283.
69. Phillips MJ, Poucell S, Oda M. Mechanisms of cholestasis. Lab Invest 1986;54:593-608.
70. Nathanson MH, Gautam A, Ng OC, Bruck R, Boyer JL. Hormonal regulation of paracellular permeability in isolated rat hepatocyte couplets. Am J Physiol 1992;262:G1079-G1086.
71. Nathanson MH, Gautam A, Bruck R, Isales CM, Boyer JL. Effects of Ca2+ agonists on cytosolic Ca2+ in isolated hepatocytes and on bile secretion in the isolated perfused rat liver. HEPATOLOGY 1992;15:107-116.
72. Yamaguchi Y, Dalle-Molle E, Hardison WG. Vasopressin and A23187 stimulate phosphorylation of myosin light chain-1 in isolated rat hepatocytes. Am J Physiol 1991;261:G312-G319.
73. Beuers U, Nathanson MH, Isales CM, Boyer JL. Tauroursodeoxycholic acid stimulates hepatocellular exocytosis and mobilizes extracellular Ca++ mechanisms defective in cholestasis. J Clin Invest 1993;92:2984-2993.
74. Bruck R, Nathanson MH, Roelofsen H, Boyer JL. Effects of protein kinase C and cytosolic Ca2+ on exocytosis in the isolated perfused rat liver. HEPATOLOGY 1994;20:1032-1040.
75. ++ entry in hepatocytes is important for PI3-kinase activation, but not for insulin receptor and IRS-1 tyrosine phosphorylation. Biochim Biophys Acta 2000;1495:14-23.
76. Yano S, Tokumitsu H, Soderling TR. Calcium promotes cell survival through CaM-K kinase activation of the protein-kinase-B pathway. Nature 1998;396:584-587.
77. Nathanson MH, Burgstahler AD, Fallon MB. Multistep mechanism of polarized Ca2+ wave patterns in hepatocytes. Am J Physiol 1994;267:G338-G349.
78. Nathanson MH, Burgstahler AD, Mennone A, Fallon MB, Gonzalez CB, Saez JC. Ca2+ waves are organized among hepatocytes in the intact organ. Am J Physiol 1995;269:G167-G171.
79. Newton AC. Regulation of the ABC kinases by phosphorylation: protein kinase C as a paradigm. Biochem J 2003;370:361-371.
80. Beuers U, Probst I, Soroka C, Boyer JL, Kullak-Ublick GA, Paumgartner G. Modulation of protein kinase C by taurolithocholic acid in isolated rat hepatocytes. HEPATOLOGY 1999;29:477-482.
81. Jones BA, Rao YP, Stravitz RT, Gores GJ. Bile salt-induced apoptosis of hepatocytes involves activation of protein kinase C. Am J Physiol 1997;272:G1109-G1115.
82. Stravitz RT, Rao YP, Vlahcevic ZR, Gurley EC, Jarvis WD, Hylemon PB. Hepatocellular protein kinase C activation by bile acids: implications for regulation of cholesterol 7 alpha-hydroxylase. Am J Physiol 1996;271:G293-G303.
83. Corasanti JG, Smith ND, Gordon ER, Boyer JL, Protein kinase C agonists inhibit bile secretion independently of effects on the microcirculation in the isolated perfused rat liver. HEPATOLOGY 1989;10:8-13.
84. Noe J, Hagenbuch B, Meier PJ, St Pierre MV. Characterization of the mouse bile salt export pump overexpressed in the baculovirus system. HEPATOLOGY 2001;33:1223-1231.
85. Rust C, Karnitz LM, Paya CV, Moscat J, Simari RD, Gores GJ. The bile acid taurochenodeoxycholate activates a phosphatidylinositol 3-kinase-dependent survival signaling cascade. J Biol Chem 2000;275:20210-20216.
86. Beuers U, Bilzer M, Chittattu A, Kullak-Ublick GA, Keppler D, Paumgartner G, Dombrowski F, et al. Tauroursodeoxycholic acid inserts the apical conjugate export pump, Mrp2, into canalicular membranes and stimulates organic anion secretion by protein kinase C-dependent mechanisms in cholestatic rat liver. HEPATOLOGY 2001;33:1206-1216.
87. Beuers U, Denk GU, Soroka CJ, Wimmer R, Rust C, Paumgartner G, Boyer JL, et al. Taurolithocholic acid exerts cholestatic effects via phosphatidylinositol-3 kinase-dependent mechanisms in perfused rat livers and rat hepatocyte couplets. J Biol Chem 2003;278:17810-17818.
88. Beuers U, Throckmorton DC, Anderson MS, Isales CM, Thasler W, Kullak-Ublick GA, Sauter G, et al. Tauroursodeoxycholic acid activates protein kinase C in isolated rat hepatocytes. Gastroenterology 1996;110:1553-1563.
89. Kubitz R, Huth C, Schmitt M, Horbach A, Kullak-Ublick G, Haussinger D. Protein kinase C-dependent distribution of the multidrug resistance protein 2 from the canalicular to the basolateral membrane in human HepG2 cells. HEPATOLOGY 2001;34:340-350.
90. Rameh LE, Cantley LC. The role of phosphoinositide 3-kinase lipid products in cell function. J Biol Chem 1999;274:8347-8350.
91. Toker A. Protein kinases as mediators of phosphoinositide 3-kinase signaling. Mol Pharmacol 2000;57:652-658.
92. Misra S, Ujházy P, Gatmaitan Z, Varticovski L, Arias IM. The role of phosphoinositide 3-kinase in taurocholate-induced trafficking of ATP-dependent canalicular transporters in rat liver. J Biol Chem 1998;273:26638-26644.
93. Kurz AK, Block C, Graf D, Dahl SV, Schliess F, Haussinger D. Phosphoinositide 3-kinase-dependent Ras activation by tauroursodesoxycholate in rat liver. Biochem J 2000;350:207-213.
94. Folli F, Alvaro D, Gigliozzi A, Bassotti C, Kahn CR, Pontiroli AE, et al. Regulation of endocytic-transcytotic pathways and bile secretion by phosphatidylinositol 3-kinase in rats. Gastroenterology 1997;113:954-965.
95. +/taurocholate cotransport polypeptide is mediated via the phosphoinositide 3-kinase signaling pathway. J Biol Chem 2000;275:29754-29760.
96. Misra S, Ujhazy P, Varticovski L, Arias IM. Phosphoinositide 3-kinase lipid products regulate ATP-dependent transport by sister of P-glycoprotein and multidrug resistance associated protein 2 in bile canalicular membrane vesicles. Proc Natl Acad Sci USA 1999;96:5814-5819.
97. Kubitz R, D'Ruso S, Keppler D, Häussinger D. Osmodependent dynamic localization of the multidrug resistance protein 2 in the rat hepatocyte canalicular membrane. Gastroenterology 1991;113:1438-1442.
98. Schmitt M, Kubitz R, Lizun S, Wettstein M, Haussinger D. Regulation of the dynamic localization of the rat Bsep gene-encoded bile salt export pump by anisoosmolarity. HEPATOLOGY 2001;33:509-518.
99. Krause U, Rider MH, Hue L. Protein kinase signalling pathway triggered by cell swelling and involved in the activation of glycogen synthase and acetyl-CoA carboxylase in isolated rat hepatocytes. J Biol Chem 1996;271:16668-16673.
100. Webster CR, Srinivasulu U, Ananthanarayanan M, Suchy FJ, Anwer MS. Protein kinase B/Akt mediates cAMP- and cell swelling-stimulated Na+/taurocholate cotransport and Ntcp translocation. J Biol Chem 2002;277:28578-28583.
101. Hernandez R, Teruel T, Lorenzo M. Akt mediates insulin induction of glucose uptake and up-regulation of GLUT4 gene expression in brown adipocytes. FEBS Lett 2001;494:225-231.
102. Standaert ML, Bandyopadhyay G, Perez L, Price D, Galloway L, Poklepovic A, Sajan MP, et al. Insulin activates protein kinases C-zeta and C-lambda by an autophosphorylation-dependent mechanism and stimulates their translocation to GLUT4 vesicles and other membrane fractions in rat adipocytes. J Biol Chem 1999;274:25308-25316.
103. Soroka CJ, Pate MK, Boyer JL. Canalicular export pumps traffic with polymeric immunoglobulin A receptor on the same microtubule-associated vesicle in rat liver. J Biol Chem 1999;274:26416-26424.
104. Wurmser AE, Gary JD, Emr SD. Phosphoinositide 3-kinases and their FYVE domain-containing effectors as regulators of vacuolar/lysosomal membrane trafficking pathways. J Biol Chem 1999;274:9129-9132.
105. Wilkinson MG, Millar JB. Control of the eukaryotic cell cycle by MAP kinase signaling pathways. FASEB J 2000;14:2147-2157.
106. Schaeffer HJ, Weber MJ. Mitogen-activated protein kinases: specific messages from ubiquitous messengers. Mol Cell Biol 1999;19:2435-2444.
107. Seger R, Krebs EG. The MAPK signaling cascade. FASEB J 1995;9:726-735.
108. Noe B, Schliess F, Wettstein M, Heinrich S, Haussinger D. Regulation of taurocholate excretion by a hypo-osmolarity-activity signal transduction pathway in rat liver. Gastroenterology 1996;110:858-865.
109. Schliess F, Kurz AK, vom Dahl S, Haussinger D. Mitogen-activated protein kinase mediate the stimulation of bile acid secretion by tauroursodeoxycholate in rat liver. Gastroenterology 1997;113:1306-1313.
110. Hafner S, Adler HS, Mischak H, Janosch P, Heidecker G, Wolfman A, Pippig S, et al. Mechanism of inhibition of Raf-1 by protein kinase A. Mol Cell Biol 1994;14:6696-6703.
111. Schliess F, Kurz AK, Haussinger D. Glucagon-induced expression of the MAP kinase phosphatase MKP-1 in rat hepatocytes. Gastroenterology 2000;118:929-936.
112. Kurz AK, Graf D, Schmitt M, Dahl SV, Haussinger D. Tauroursodesoxycholate-induced choleresis involves p38(MAPK) activation and translocation of the bile salt export pump in rats. Gastroenterology 2001;121:407-419.
113. Lazaridis KN, Gores GJ, Lindor KD. Ursodeoxycholic acid mechanisms of action and clinical use in hepatobiliary disorders. J Hepatol 2001;35:134-146.
114. Hamm-Alvarez SF, Wei X, Bernbdt N, Runnegar M. Protein phosphatases independently regulate vesicle movement and microtubule subpopulations in hepatocytes. Am J Physiol 1996;271:C929-C943.
115. +/taurocholate cotransport. J Biol Chem 1998;273:30039-30045.
116. Glavy JS, Wu SM, Wang PJ, Orr GA, Wolkoff AW. Down-regulation by extracellular ATP of rat hepatocyte organic anion transport is mediated by serine phosphorylation of Oatp 1. J Biol Chem 2000;275:1479-1484.