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Elevated expression of protein kinase C delta induces cell scattering upon serum deprivation.
- Source :
-
Journal of cell science [J Cell Sci] 2010 Sep 01; Vol. 123 (Pt 17), pp. 2901-13. Date of Electronic Publication: 2010 Aug 03. - Publication Year :
- 2010
-
Abstract
- Tumor metastasis might be evoked in response to microenvironmental stress, such as a shortage of oxygen. Although the cellular response to hypoxia has been well established, we know little about how tumors adapt themselves to deprivation of growth factor. Protein kinase Cdelta (PKCdelta), a stress-sensitive protein kinase, has been implicated in tumor progression. In this study, we demonstrate that elevated expression of PKCdelta in Madin-Darby canine kidney cells induces a scatter response upon serum starvation, a condition that mimics growth-factor deprivation. Serum starvation stimulates the catalytic activity and Y311 phosphorylation of PKCdelta through reactive oxygen species (ROS) and the Src family kinases. Mutation of PKCdelta at Y311 and Y322, both of which are phosphorylation sites for Src, impairs its activation and ability to promote cell scattering upon serum deprivation. Once activated by ROS, PKCdelta itself activates ROS production at least partially through NADPH oxidase. In addition, the c-Jun N-terminal kinase is identified as a crucial downstream mediator of ROS and PKCdelta for induction of cell scattering upon serum deprivation. We demonstrate that the C1B domain of PKCdelta is essential not only for its localization at the Golgi complex, but also for its activation and ability to induce cell scattering upon serum deprivation. Finally, depletion of PKCdelta in human bladder carcinoma T24 cells restores their cell-cell contacts, which thereby reverses a scattered growth pattern to an epithelial-like growth pattern. Collectively, our results suggest that elevated expression of PKCdelta might facilitate the scattering of cells in order to escape stress induced by growth-factor deprivation.
- Subjects :
- Animals
Cell Line
Culture Media, Serum-Free
Dogs
Golgi Apparatus enzymology
Humans
Kidney cytology
Kidney enzymology
MAP Kinase Kinase 4 metabolism
NADPH Oxidases metabolism
Phosphorylation
Protein Kinase C-delta biosynthesis
Protein Kinase C-delta deficiency
Reactive Oxygen Species metabolism
Urinary Bladder Neoplasms enzymology
Urinary Bladder Neoplasms pathology
src-Family Kinases metabolism
Cell Communication physiology
Protein Kinase C-delta metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1477-9137
- Volume :
- 123
- Issue :
- Pt 17
- Database :
- MEDLINE
- Journal :
- Journal of cell science
- Publication Type :
- Academic Journal
- Accession number :
- 20682636
- Full Text :
- https://doi.org/10.1242/jcs.069765