@article {47674,
	title = {Bile acid stimulates hepatocyte polarization through a cAMP-Epac-MEK-LKB1-AMPK pathway.},
	journal = {Proceedings of the National Academy of Sciences of the United States of America},
	volume = {108},
	year = {2011},
	month = {2011 Jan 25},
	pages = {1403-8},
	abstract = {<p>This study describes a unique function of taurocholate in bile canalicular formation involving signaling through a cAMP-Epac-MEK-Rap1-LKB1-AMPK pathway. In rat hepatocyte sandwich cultures, polarization was manifested by sequential progression of bile canaliculi from small structures to a fully branched network. Taurocholate accelerated canalicular network formation and concomitantly increased cAMP, which were prevented by adenyl cyclase inhibitor. The cAMP-dependent PKA inhibitor did not prevent the taurocholate effect. In contrast, activation of Epac, another cAMP downstream kinase, accelerated canalicular network formation similar to the effect of taurocholate. Inhibition of Epac downstream targets, Rap1 and MEK, blocked the taurocholate effect. Taurocholate rapidly activated MEK, LKB1, and AMPK, which were prevented by inhibition of adenyl cyclase or MEK. Our previous study showed that activated-LKB1 and AMPK participate in canalicular network formation. Linkage between bile acid synthesis, hepatocyte polarization, and regulation of energy metabolism is likely important in normal hepatocyte development and disease.</p>
},
	keywords = {Adenylate Kinase, Animals, Bile Acids and Salts, Blotting, Western, Cell Polarity, Cells, Cultured, Chenodeoxycholic Acid, Cholagogues and Choleretics, Cyclic AMP, Dose-Response Relationship, Drug, Green Fluorescent Proteins, Guanine Nucleotide Exchange Factors, Hepatocytes, Imines, Microscopy, Confocal, Mitogen-Activated Protein Kinase Kinases, Models, Biological, Protein-Serine-Threonine Kinases, rap1 GTP-Binding Proteins, Rats, Rats, Sprague-Dawley, Signal Transduction, Taurocholic Acid, Ursodeoxycholic Acid},
	issn = {1091-6490},
	doi = {10.1073/pnas.1018376108},
	author = {Fu, Dong and Wakabayashi, Yoshiyuki and Lippincott-Schwartz, Jennifer and Arias, Irwin M}
}
