Staff Publications

Staff Publications

  • external user (warningwarning)
  • Log in as
  • language uk
  • About

    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

    We have a manual that explains all the features 

Record number 433446
Title Diacylglycerol kinase counteracts protein kinase C-mediated inactivation of the EGF receptor
Author(s) Baal, J. van; Widt, J. de; Divecha, N.; Blitterswijk, W.J. van
Source International Journal of Biochemistry and Cell Biology 44 (2012)11. - ISSN 1357-2725 - p. 1791 - 1799.
DOI https://doi.org/10.1016/j.biocel.2012.06.021
Department(s) Animal Nutrition
WIAS
Publication type Refereed Article in a scientific journal
Publication year 2012
Keyword(s) growth-factor receptor - signal-transduction - coupled receptors - phosphorylation - cells - src - transactivation - activation - mechanisms - expression
Abstract 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 DGK 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, DGK physically interacted with the EGFR and became tyrosine-phosphorylated upon EGFR stimulation. Overexpression of DGK attenuated the bradykinin-stimulated, PKC-mediated EGFR phosphorylation at Thr654, and enhanced the phosphorylation at Tyr845 and Tyr1068. SiRNA-induced DGK downregulation enhanced this PKC-mediated Thr654 phosphorylation. Our data indicate that DGK translocation and activity is regulated by the concerted activity of EGFR and PKC and that DGK attenuates PKC-mediated Thr654 phosphorylation that is linked to desensitisation of EGFR signaling
Comments
There are no comments yet. You can post the first one!
Post a comment
 
Please log in to use this service. Login as Wageningen University & Research user or guest user in upper right hand corner of this page.