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• W2021760249 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 Cδ (PKCδ), a stress-sensitive protein kinase, has been implicated in tumor progression. In this study, we demonstrate that elevated expression of PKCδ 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 PKCδ through reactive oxygen species (ROS) and the Src family kinases. Mutation of PKCδ 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, PKCδ 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 PKCδ for induction of cell scattering upon serum deprivation. We demonstrate that the C1B domain of PKCδ 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 PKCδ 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 PKCδ might facilitate the scattering of cells in order to escape stress induced by growth-factor deprivation." @default.
• W2021760249 created "2016-06-24" @default.
• W2021760249 creator A5016185746 @default.
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• W2021760249 creator A5082443098 @default.
• W2021760249 creator A5085222370 @default.
• W2021760249 date "2010-09-01" @default.
• W2021760249 modified "2023-09-23" @default.
• W2021760249 title "Elevated expression of protein kinase Cδ induces cell scattering upon serum deprivation" @default.
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• W2021760249 doi "https://doi.org/10.1242/jcs.069765" @default.
• W2021760249 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20682636" @default.
• W2021760249 hasPublicationYear "2010" @default.
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