Publication

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

Wojtal, K. A., Diskar, M., Herberg, F. W., Hoekstra, D. & van Ijzendoorn, S. C. D., 31-Jul-2009, In : The Journal of Biological Chemistry. 284, 31, p. 20773-20780 8 p.

Research output: Contribution to journalArticleAcademicpeer-review

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)20773-20780
Number of pages8
JournalThe Journal of Biological Chemistry
Volume284
Issue number31
Publication statusPublished - 31-Jul-2009

    Keywords

  • POLARIZED SPHINGOLIPID TRANSPORT, FETAL LIVER DEVELOPMENT, ENERGY-TRANSFER BRET, CELL POLARITY, ONCOSTATIN-M, CYCLIC-AMP, HEPG2 CELLS, CAMP-KINASE, SUBAPICAL COMPARTMENT, MEMBRANE BIOGENESIS

ID: 4928320