Journal article

Regulatory Subunit I-controlled Protein Kinase A Activity Is Required for Apical Bile Canalicular Lumen Development in Hepatocytes



Publication Details
Authors:
Wojtal, K.; Diskar, M.; Herberg, F.; Hoekstra, D.; van Ijzendoorn, S.

Publication year:
2009
Pages range :
20773-20780
Volume number:
284
Start page:
20773
End page:
20780
ISSN:
0021-9258


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.

Last updated on 2023-21-08 at 12:58