ArticleMolecular and cellular biology2002
Tyrosine phosphorylation of protein kinase Cdelta is essential for its apoptotic effect in response to etoposide.
Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 195 citations in OpenAlex.
- Modelling the Full-Length Inactive PKC-δ Structure to Explore Regulatory Accessibility and Selective Targeting Opportunities.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Protein Kinase C Family: Structures, Biological Functions, Diseases, and Pharmaceutical Interventions.MedComm · 2025Review
- Fyn Kinase-Mediated PKCδ Y311 Phosphorylation Induces Dopaminergic Degeneration in Cell Culture and Animal Models: Implications for the Identification of a New Pharmacological Target for Parkinson's Disease.Frontiers in pharmacology · 2021Article
- Phosphorylation controls RNA binding and transcription by the influenza virus polymerase.PLoS pathogens · 2020Article
- Lanatoside C, a cardiac glycoside, acts through protein kinase Cδ to cause apoptosis of human hepatocellular carcinoma cells.Scientific reports · 2017Article
- Multifunctional roles of PKCδ: Opportunities for targeted therapy in human disease.Pharmacology & therapeutics · 2016Review
- Protein kinase Cα mediates erlotinib resistance in lung cancer cells.Molecular pharmacology · 2015Article
- Distinct contribution of protein kinase Cδ and protein kinase Cε in the lifespan and immune response of human blood monocyte subpopulations.Immunology · 2015Article
- Molecular systems pharmacology: isoelectric focusing signature of protein kinase Cδ provides an integrated measure of its modulation in response to ligands.Journal of medicinal chemistry · 2014Article
- MiR-181a confers resistance of cervical cancer to radiation therapy through targeting the pro-apoptotic PRKCD gene.Oncogene · 2013Article
- Differential signaling of the GnRH receptor in pituitary gonadotrope cell lines and prostate cancer cell lines.Molecular and cellular endocrinology · 2013Article
- 67-kDa laminin receptor increases cGMP to induce cancer-selective apoptosis.The Journal of clinical investigation · 2013Article
- Isozyme-specific interaction of protein kinase Cδ with mitochondria dissected using live cell fluorescence imaging.The Journal of biological chemistry · 2012Article
- Star-PAP control of BIK expression and apoptosis is regulated by nuclear PIPKIα and PKCδ signaling.Molecular cell · 2012Article
- DNA damage response signaling triggers nuclear localization of the chicken anemia virus protein Apoptin.Journal of virology · 2011Article
- Environmental neurotoxic pesticide dieldrin activates a non receptor tyrosine kinase to promote PKCδ-mediated dopaminergic apoptosis in a dopaminergic neuronal cell model.Neurotoxicology · 2011Article
- p23/Tmp21 associates with protein kinase Cdelta (PKCdelta) and modulates its apoptotic function.The Journal of biological chemistry · 2011Article
- Protein kinase Cδ regulates vaccinia-related kinase 1 in DNA damage-induced apoptosis.Molecular biology of the cell · 2011Article
- Differential regulation of gene expression by protein kinase C isozymes as determined by genome-wide expression analysis.The Journal of biological chemistry · 2011Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein kinase Cdelta (PKCdelta) is involved in the apoptosis of various cells in response to diverse stimuli. In this study, we characterized the role of PKCdelta in the apoptosis of C6 glioma cells in response to etoposide. We found that etoposide induced apoptosis in the C6 cells within 24 to 48 h and arrested the cells in the G(1)/S phase of the cell cycle. Overexpression of PKCdelta increased the apoptotic effect induced by etoposide, whereas the PKCdelta selective inhibitor rottlerin and the PKCdelta dominant-negative mutant K376R reduced this effect compared to control cells. Etoposide-induced tyrosine phosphorylation of PKCdelta and its translocation to the nucleus within 3 h was followed by caspase-dependent cleavage of the enzyme. Using PKC chimeras, we found that both the regulatory and catalytic domains of PKCdelta were necessary for its apoptotic effect. The role of tyrosine phosphorylation of PKCdelta in the effects of etoposide was examined using cells overexpressing a PKCdelta mutant in which five tyrosine residues were mutated to phenylalanine (PKCdelta5). These cells exhibited decreased apoptosis in response to etoposide compared to cells overexpressing PKCdelta. Likewise, activation of caspase 3 and the cleavage of the PKCdelta5 mutant were significantly lower in cells overexpressing PKCdelta5. Using mutants of PKCdelta altered at individual tyrosine residues, we identified tyrosine 64 and tyrosine 187 as important phosphorylation sites in the apoptotic effect induced by etoposide. Our results suggest a role of PKCdelta in the apoptosis induced by etoposide and implicate tyrosine phosphorylation of PKCdelta as an important regulator of this effect.
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