Article abstract
Nature Cell Biology
Published online: 6 July 2008 | doi:10.1038/ncb1749
The regulated assembly of a PKC
complex controls the completion of cytokinesis
Adrian T. Saurin1, Joanne Durgan1, Angus J. Cameron1, Amir Faisal1, Michael S. Marber2 & Peter J. Parker1,3
Abstract
The cell cycle is exquisitely controlled by multiple sequential regulatory inputs to ensure fidelity. Here we demonstrate that the final step in division, the physical separation of daughter cells, is controlled by a member of the PKC gene superfamily. Specifically, we have identified three phosphorylation sites within PKC
that control its association with 14-3-3. These phosphorylations are executed by p38 MAP kinase (Ser 350), GSK3 (Ser 346) and PKC itself (Ser 368). Integration of these signals is essential during mitosis because mutations that prevent phosphorylation of PKC and/or PKC binding to 14-3-3 also cause defects in the completion of cytokinesis. Using chemical genetic and dominant-negative approaches it is shown that selective inhibition of PKC halts cells at the final stages of separation. This arrest is associated with persistent RhoA activation at the midbody and a delay in actomyosin ring dissociation. This study therefore identifies a new regulatory mechanism that controls exit from cytokinesis, which has implications for carcinogenesis.
- Protein Phosphorylation Laboratory, London Research Institute, Cancer Research UK, London, WC2A 3PX, UK.
- Department of Cardiology, The Cardiovascular Division, King's College London, The Rayne Institute, St Thomas' Hospital, London, SE1 7EH, UK.
- Division of Cancer Studies, King's College London, New Hunt's House, St Thomas Street, London SE1 1UL, UK.
Correspondence to: Peter J. Parker1,3 e-mail: peter.parker@cancer.org.uk