Oncostatin M-stimulated apical plasma membrane biogenesis requires p27(Kip1)-regulated cell cycle dynamics.
Oncostatin M regulates membrane traffic and stimulates apicalization of the cell surface in hepatoma cells in a protein kinase A-dependent manner. Here, we show that oncostatin M enhances the expression of the cyclin-dependent kinase (cdk)2 inhibitor p27(Kip1), which inhibits G(1)-S phase progression. Forced G(1)-S-phase transition effectively renders presynchronized cells insensitive to the apicalization-stimulating effect of oncostatin M. G(1)-S-phase transition prevents oncostatin M-mediated recruitment of protein kinase A to the centrosomal region and precludes the oncostatin M-mediated activation of a protein kinase A-dependent transport route to the apical surface, which exits the subapical compartment (SAC). This transport route has previously been shown to be crucial for apical plasma membrane biogenesis. Together, our data indicate that oncostatin M-stimulated apicalization of the cell surface is critically dependent on the ability of oncostatin M to control p27(Kip1)/cdk2-mediated G(1)-S-phase progression and suggest that the regulation of apical plasma membrane-directed traffic from SAC is coupled to centrosome-associated signaling pathways.
Van IJzendoorn
Sven C D
SC
Department of Membrane Cell Biology, University of Groningen, 9713 AV, Groningen, The Netherlands. s.c.d.van.ijzendoorn@med.rug.nl
Théard
Delphine
D
Van Der Wouden
Johanna M
JM
Visser
Willy
W
Wojtal
Kacper A
KA
Hoekstra
Dick
D
D002451:Cell Compartmentation; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism*; D016764:Cell Polarity; D018385:Centrosome / Q000378:metabolism; D003470:Culture Media; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016193:G1 Phase; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism; D008954:Models, Biological; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology*; D016196:S Phase; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D018797:Cell Cycle Proteins; D003470:Culture Media; D008563:Membrane Lipids; C508351:OSM protein, human; D010455:Peptides; D025521:Tumor Suppressor Proteins; D053683:Oncostatin M; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017868:Cyclic AMP-Dependent Protein Kinases