ArticleThe Journal of biological chemistry2014
Inhibiting tyrosine phosphorylation of protein kinase Cδ (PKCδ) protects the salivary gland from radiation damage.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Protein Kinase C-delta (PKCδ) in Neurodegeneration and Cerebral Ischemia: Molecular Mechanisms and Therapeutic Implications.Cell biochemistry and biophysics · 2026Review
- The C2 Domain of PKC‑δ as a Dominant-Negative Modulator of Breast Cancer Cell Survival and Chemosensitivity.ACS omega · 2025Article
- Modelling the Full-Length Inactive PKC-δ Structure to Explore Regulatory Accessibility and Selective Targeting Opportunities.Pharmaceuticals (Basel, Switzerland) · 2025Article
- PKCδ Regulates DNA Damage and Cell Death through a SIRT6/Nrf2-dependent Antioxidant Response.Molecular cancer research : MCR · 2025Article
- Novel Ser74 of NF-κB/IκBα phosphorylated by MAPK/ERK regulates temperature adaptation in oysters.Cell communication and signaling : CCS · 2024Article
- PKCδ Regulates Chromatin Remodeling and DNA Repair through SIRT6.Molecular cancer research : MCR · 2024Article
- Long-term functional regeneration of radiation-damaged salivary glands through delivery of a neurogenic hydrogel.Science advances · 2022Article
- Mechanism, Prevention, and Treatment of Radiation-Induced Salivary Gland Injury Related to Oxidative Stress.Antioxidants (Basel, Switzerland) · 2021Review
- Mechanisms of radiation-induced endothelium damage: Emerging models and technologies.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2021Review
- Radiation-Induced Salivary Gland Dysfunction: Mechanisms, Therapeutics and Future Directions.Journal of clinical medicine · 2020Review
- Functional proteomic analysis reveals roles for PKCδ in regulation of cell survival and cell death: Implications for cancer pathogenesis and therapy.Advances in biological regulation · 2020Article
- Protein Kinase C-Delta (PKCδ) Tyrosine Phosphorylation is a Critical Regulator of Neutrophil-Endothelial Cell Interaction in Inflammation.Shock (Augusta, Ga.) · 2019Article
- EGF receptor and PKCδ kinase activate DNA damage-induced pro-survival and pro-apoptotic signaling via biphasic activation of ERK and MSK1 kinases.The Journal of biological chemistry · 2019Article
- SCF/c-KIT signaling promotes mucus secretion of colonic goblet cells and development of mucinous colorectal adenocarcinoma.American journal of cancer research · 2018Article
- Tyrosine Kinase Inhibitors Protect the Salivary Gland from Radiation Damage by Inhibiting Activation of Protein Kinase C-δ.Molecular cancer therapeutics · 2017Article
- Co-dependency of PKCδ and K-Ras: inverse association with cytotoxic drug sensitivity in KRAS mutant lung cancer.Oncogene · 2017Article
- Insulin-Like Growth Factor-1-Mediated DNA Repair in Irradiated Salivary Glands Is Sirtuin-1 Dependent.Journal of dental research · 2017Article
- Dasatinib enhances tumor growth in gemcitabine-resistant orthotopic bladder cancer xenografts.BMC research notes · 2016Article
- Protein kinase Cδ upregulation in microglia drives neuroinflammatory responses and dopaminergic neurodegeneration in experimental models of Parkinson's disease.Neurobiology of disease · 2016Article
- Multifunctional roles of PKCδ: Opportunities for targeted therapy in human disease.Pharmacology & therapeutics · 2016Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Radiation therapy for head and neck cancer can result in extensive damage to normal adjacent tissues such as the salivary gland and oral mucosa. We have shown previously that tyrosine phosphorylation at Tyr-64 and Tyr-155 activates PKCδ in response to apoptotic stimuli by facilitating its nuclear import. Here we have identified the tyrosine kinases that mediate activation of PKCδ in apoptotic cells and have explored the use of tyrosine kinase inhibitors for suppression of irradiation-induced apoptosis. We identify the damage-inducible kinase, c-Abl, as the PKCδ Tyr-155 kinase and c-Src as the Tyr-64 kinase. Depletion of c-Abl or c-Src with shRNA decreased irradiation- and etoposide-induced apoptosis, suggesting that inhibitors of these kinases may be useful therapeutically. Pretreatment with dasatinib, a broad spectrum tyrosine kinase inhibitor, blocked phosphorylation of PKCδ at both Tyr-64 and Tyr-155. Expression of "gate-keeper" mutants of c-Abl or c-Src that are active in the presence of dasatinib restored phosphorylation of PKCδ at Tyr-155 and Tyr-64, respectively. Imatinib, a c-Abl-selective inhibitor, also specifically blocked PKCδ Tyr-155 phosphorylation. Dasatinib and imatinib both blocked binding of PKCδ to importin-α and nuclear import, demonstrating that tyrosine kinase inhibitors can inhibit nuclear accumulation of PKCδ. Likewise, pretreatment with dasatinib also suppressed etoposide and radiation induced apoptosis in vitro. In vivo, pre-treatment of mice with dasatinib blocked radiation-induced apoptosis in the salivary gland by >60%. These data suggest that tyrosine kinase inhibitors may be useful prophylactically for protection of nontumor tissues in patients undergoing radiotherapy of the head and neck.
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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.