Regulatory subunit I-controlled protein kinase A activity is required for apical bile canalicular lumen development in hepatocytes

Kacper A Wojtal, Mandy Diskar, Friedrich W Herberg, Dick Hoekstra, Sven C D van Ijzendoorn

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3 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)20773-80
Number of pages8
JournalJournal of Biological Chemistry
Issue number31
Publication statusPublished - 31 Jul 2009


  • Adenylate Cyclase
  • Bile Canaliculi
  • Cell Line, Tumor
  • Cell Nucleus
  • Cell Polarity
  • Cell Survival
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit
  • Cyclic AMP-Dependent Protein Kinase RIalpha Subunit
  • Energy Transfer
  • Enzyme Activation
  • Enzyme Activators
  • Enzyme Inhibitors
  • Hepatocytes
  • Holoenzymes
  • Humans
  • Isoenzymes
  • Mitogen-Activated Protein Kinase 3
  • Oncostatin M
  • Phosphorylation
  • Recombinant Fusion Proteins


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