ArticleThe Journal of biological chemistry2010
Diacylglycerol kinase delta and protein kinase C(alpha) modulate epidermal growth factor receptor abundance and degradation through ubiquitin-specific protease 8.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Kinectin1 depletion promotes EGFR degradation via the ubiquitin-proteosome system in cutaneous squamous cell carcinoma.Cell death & disease · 2021Article
- The complexities of PKCα signaling in cancer.Advances in biological regulation · 2021Review
- Predicting Panel of Metabolism and Immune-Related Genes for the Prognosis of Human Ovarian Cancer.Frontiers in cell and developmental biology · 2021Article
- Epitope mapping of an anti-diacylglycerol kinase delta monoclonal antibody DdMab-1.Biochemistry and biophysics reports · 2020Article
- Beyond Lipid Signaling: Pleiotropic Effects of Diacylglycerol Kinases in Cellular Signaling.International journal of molecular sciences · 2020Review
- Regulation of Deubiquitinating Enzymes by Post-Translational Modifications.International journal of molecular sciences · 2020Review
- Molecular Pathways: Targeting Diacylglycerol Kinase Alpha in Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Article
- A kinase inhibitor screen reveals protein kinase C-dependent endocytic recycling of ErbB2 in breast cancer cells.The Journal of biological chemistry · 2014Article
- Overexpression of diacylglycerol kinase η enhances Gαq-coupled G protein-coupled receptor signaling.Molecular pharmacology · 2014Article
- Diacylglycerol kinase η modulates oncogenic properties of lung cancer cells.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2014Article
- Diacylglycerol kinase δ modulates Akt phosphorylation through pleckstrin homology domain leucine-rich repeat protein phosphatase 2 (PHLPP2).The Journal of biological chemistry · 2013Article
- Sustained activation of protein kinase C induces delayed phosphorylation and regulates the fate of epidermal growth factor receptor.PloS one · 2013Article
- Balanced ubiquitination determines cellular responsiveness to extracellular stimuli.Cellular and molecular life sciences : CMLS · 2012Review
- Identification of kinases regulating prostate cancer cell growth using an RNAi phenotypic screen.PloS one · 2012Article
- PTMs in conversation: activity and function of deubiquitinating enzymes regulated via post-translational modifications.Cell biochemistry and biophysics · 2011Review
- Diacylglycerol kinases in membrane trafficking.Cellular logisticsReview
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Many human epithelial cancers are characterized by abnormal activation of the epidermal growth factor receptor (EGFR), which is often caused by its excessive expression in tumor cells. The abundance of EGFR is modulated, in part, by its ubiquitination, which targets it for degradation. The components responsible for adding ubiquitin to EGFR are well characterized, but this is a reversible process, and the mechanisms that modulate the removal of ubiquitin from the EGFR are not well known. We found that de-ubiquitination of EGFR was regulated by diacylglycerol kinase delta (DGKdelta), a lipid kinase that terminates diacylglycerol signaling. In DGKdelta-deficient cells, ubiquitination of EGFR was enhanced, which attenuated the steady-state levels of EGFR and promoted its ligand-induced degradation. These effects were not caused by changes in the ubiquitinating apparatus, but instead were due to reduced expression of the de-ubiquitinase, ubiquitin-specific protease 8 (USP8). Depletion of protein kinase Calpha (PKCalpha), a target of diacylglycerol, rescued the levels of USP8 and normalized EGFR degradation in DGKdelta-deficient cells. Moreover, the effects of PKCalpha were caused by its inhibition of Akt, which stabilizes USP8. Our data indicate a novel mechanism where DGKdelta and PKCalpha modulate the levels of ubiquitinated EGFR through Akt and USP8.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.