Diacylglycerol kinase counteracts protein kinase C-mediated inactivation of the EGF receptor
| Autor: | Jürgen van Baal, Wim J. van Blitterswijk, John de Widt, Nullin Divecha |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
signal-transduction
Diacylglycerol Kinase Animal Nutrition Green Fluorescent Proteins Uridine Triphosphate Endosomes Bradykinin growth-factor receptor Biochemistry Growth factor receptor transactivation Cell Line Tumor expression Humans Gene Silencing Phosphotyrosine Protein Kinase C Protein kinase C src Diacylglycerol kinase mechanisms Chemistry phosphorylation Cell Membrane Cell Biology Molecular biology Diervoeding Enzyme Activation ErbB Receptors Protein Transport coupled receptors HEK293 Cells Phosphothreonine WIAS Tetradecanoylphorbol Acetate Cyclin-dependent kinase 8 Phosphorylation cells activation Signal transduction A431 cells Protein Binding Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | International Journal of Biochemistry and Cell Biology 44 (2012) 11 International Journal of Biochemistry and Cell Biology, 44(11), 1791-1799 |
| ISSN: | 1357-2725 |
| Popis: | Epidermal growth factor receptor (EGFR) activation is negatively regulated by protein kinase C (PKC) signaling. Stimulation of A431 cells with EGF, bradykinin or UTP increased EGFR phosphorylation at Thr654 in a PKC-dependent manner. Inhibition of PKC signaling enhanced EGFR activation, as assessed by increased phosphorylation of Tyr845 and Tyr1068 residues of the EGFR. Diacylglycerol is a physiological activator of PKC that can be removed by diacylglycerol kinase (DGK) activity. We found, in A431 and HEK293 cells, that the DGKθ isozyme translocated from the cytosol to the plasma membrane, where it co-localized with the EGFR and subsequently moved into EGFR-containing intracellular vesicles. This translocation was dependent on both activation of EGFR and PKC signaling. Furthermore, DGKθ physically interacted with the EGFR and became tyrosine-phosphorylated upon EGFR stimulation. Overexpression of DGKθ attenuated the bradykinin-stimulated, PKC-mediated EGFR phosphorylation at Thr654, and enhanced the phosphorylation at Tyr845 and Tyr1068. SiRNA-induced DGKθ downregulation enhanced this PKC-mediated Thr654 phosphorylation. Our data indicate that DGKθ translocation and activity is regulated by the concerted activity of EGFR and PKC and that DGKθ attenuates PKC-mediated Thr654 phosphorylation that is linked to desensitisation of EGFR signaling. |
| Databáze: | OpenAIRE |
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