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PMID: 17494870 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Anchoring of protein kinase A-regulatory subunit IIalpha to subapically positioned centrosomes mediates apical bile canalicular lumen development in response to oncostatin M but not cAMP.

Molecular biology of the cell ·Vol. 18 ·No. 7 ·2007-07-00 ·Pages 2745-54

Wojtal KA, Hoekstra D, van Ijzendoorn SC

Abstract

Oncostatin M and cAMP signaling stimulate apical surface-directed membrane trafficking and apical lumen development in hepatocytes, both in a protein kinase A (PKA)-dependent manner. Here, we show that oncostatin M, but not cAMP, promotes the A-kinase anchoring protein (AKAP)-dependent anchoring of the PKA regulatory subunit (R)IIalpha to subapical centrosomes and that this requires extracellular signal-regulated kinase 2 activation. Stable expression of the RII-displacing peptide AKAP-IS, but not a scrambled peptide, inhibits the association of RIIalpha with centrosomal AKAPs and results in the repositioning of the centrosome from a subapical to a perinuclear location. Concomitantly, common endosomes, but not apical recycling endosomes, are repositioned from a subapical to a perinuclear location, without significant effects on constitutive or oncostatin M-stimulated basolateral-to-apical transcytosis. Importantly, however, the expression of the AKAP-IS peptide completely blocks oncostatin M-, but not cAMP-stimulated apical lumen development. Together, the data suggest that centrosomal anchoring of RIIalpha and the interrelated subapical positioning of these centrosomes is required for oncostatin M-, but not cAMP-mediated, bile canalicular lumen development in a manner that is uncoupled from oncostatin M-stimulated apical lumen-directed membrane trafficking. The results also imply that multiple PKA-mediated signaling pathways control apical lumen development and that subapical centrosome positioning is important in some of these pathways.

MeSH Terms
Adaptor Proteins, Signal Transducing/pharmacology Bile Canaliculi/drug effects,enzymology Bucladesine/pharmacology Cell Line, Tumor Cell Membrane/drug effects,enzymology Cell Polarity/drug effects Centrosome/drug effects,enzymology Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors,metabolism Endocytosis/drug effects Endosomes/drug effects Humans Oncostatin M/pharmacology Protein Binding/drug effects Subcellular Fractions/drug effects
Chemicals
Adaptor Proteins, Signal Transducing Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit PRKAR2A protein, human Oncostatin M Bucladesine Cyclic AMP-Dependent Protein Kinases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Wojtal Kacper A
Department of Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Hoekstra Dick
van Ijzendoorn Sven C D
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
Published
2007-07-00
Epub
2007-00-09
Pages
2745-54
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC1924835
Subset
IM
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