@article{a2009regulatory, abstract = {Signaling via cAMP plays an important role in apical cell surface dynamics in epithelial cells. In hepatocytes, elevated levels of cAMP as well as extracellular oncostatin M stimulate apical lumen development in a manner that depends on protein kinase A (PKA) activity. However, neither the identity of PKA isoforms involved nor the mechanisms of the cross-talk between oncostatin M and cAMP/PKA signaling pathways have been elucidated. Here we demonstrate that oncostatin M and PKA signaling converge at the level of the PKA holoenzyme downstream of oncostatin M-stimulated MAPK activation. Experiments were performed with chemically modified cAMP analogues that preferentially target regulatory subunit (R) I or RII holoenzymes, respectively, in hepatocytes. The data suggest that the dissociation of RI- but not RII-containing holoenzymes, as well as catalytic activity of PKA, is required for apical lumen development in response to elevated levels of cAMP and oncostatin M. However, oncostatin M signaling does not stimulate PKA holoenzyme dissociation in living cells. Based on pharmacological and cell biological studies, it is concluded that RI-controlled PKA activity is essential for cAMP- and oncostatin M-stimulated development of apical bile canalicular lumens.}, annote = {Wojtal, Kacper A Diskar, Mandy Herberg, Friedrich W Hoekstra, Dick van Ijzendoorn, Sven C D Research Support, Non-U.S. Gov't United States The Journal of biological chemistry J Biol Chem. 2009 Jul 31;284(31):20773-80. Epub 2009 May 22.}, author = {Wojtal, K. A. and Diskar, M. and Herberg, F. W. and Hoekstra, D. and van Ijzendoorn, S. C.}, edition = {2009/05/26}, interhash = {734427862c7c2242b354f6d2d8af53b3}, intrahash = {0a9f721e8775d77b2317403ea0af637f}, isbn = {1083-351X (Electronic) 0021-9258 (Linking)}, journal = {J Biol Chem}, pages = {20773-80}, series = 31, title = {Regulatory subunit I-controlled protein kinase A activity is required for apical bile canalicular lumen development in hepatocytes}, url = {http://www.ncbi.nlm.nih.gov/pubmed/19465483}, volume = 284, year = 2009 }