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MBC in Press, published online ahead of print July 7, 2004
Mol. Biol. Cell 10.1091/mbc.E04-03-0201

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Submitted on March 11, 2004
Revised on June 17, 2004
Accepted on June 24, 2004

Oncostatin M-Stimulated Apical Plasma Membrane Biogenesis Requires p27Kip1-Regulated Cell Cycle Dynamics

Sven C. D. van IJzendoorn*{dagger}, Delphine Théard*, Johanna M. van der Wouden, Willy Visser, Kacper A. Wojtal, and Dick Hoekstra

Department of Membrane Cell Biology, University of Groningen, 9713 AV, Groningen, The Netherlands

Monitoring Editor: Keith Mostov

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 p27Kip1, which inhibits G1-S phase progression. Forced G1-S-phase transition effectively renders presynchronized cells insensitive to the apicalization-stimulating effect of oncostatin M. G1-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. Taken together, our data indicate that oncostatin M-stimulated apicalization of the cell surface is critically dependent on the ability of oncostatin M to control p27Kip1/cdk2-mediated G1-S-phase progression, and suggest that the regulation of apical plasma membrane-directed traffic from SAC is coupled to centrosome-associated signaling pathways.

*These authors contributed equally to this work.

{dagger}Corresponding author. E-mail: s.c.d.van.ijzendoorn{at}med.rug.nl




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