%0 Journal Article
%1 a2009regulatory
%A Wojtal, K. A.
%A Diskar, M.
%A Herberg, F. W.
%A Hoekstra, D.
%A van Ijzendoorn, S. C.
%B 31
%D 2009
%J J Biol Chem
%K Herberg myown
%P 20773-80
%T Regulatory subunit I-controlled protein kinase A activity is required for apical bile canalicular lumen development in hepatocytes
%U http://www.ncbi.nlm.nih.gov/pubmed/19465483
%V 284
%X 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.
%Z 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.
%7 2009/05/26