ArticleThe Journal of biological chemistry2015
Epidermal Growth Factor-dependent Activation of the Extracellular Signal-regulated Kinase Pathway by DJ-1 Protein through Its Direct Binding to c-Raf Protein.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 37 citations in OpenAlex.
- Mechanisms of Programmed Cell Death in Sodium Iodate-Driven Retinal Degeneration and the Role of DJ-1.International journal of molecular sciences · 2026Article
- Protein kinases in neurodegenerative diseases: current understandings and implications for drug discovery.Signal transduction and targeted therapy · 2025Review
- High glucose couples DJ-1 with PTEN to activate PDGFRβ for renal proximal tubular cell injury.PloS one · 2025Article
- PARK7 deficiency inhibits fatty acid β-oxidation via PTEN to delay liver regeneration after hepatectomy.Clinical and translational medicine · 2022Article
- DJ-1 inhibits microglial activation and protects dopaminergic neurons in vitro and in vivo through interacting with microglial p65.Cell death & disease · 2021Article
- The C terminus of DJ-1 determines its homodimerization, MGO detoxification activity and suppression of ferroptosis.Acta pharmacologica Sinica · 2021Article
- Knockdown of the DJ-1 (Molecular therapy oncolytics · 2021Article
- PARK7 maintains the stemness of glioblastoma stem cells by stabilizing epidermal growth factor receptor variant III.Oncogene · 2021Article
- Correlations among Pulmonary DJ-1, VDR and Nrf-2 in patients with Chronic Obstructive Pulmonary Disease: A Case-control Study.International journal of medical sciences · 2021Observational
- Progress in the molecular pathogenesis and nucleic acid therapeutics for Parkinson's disease in the precision medicine era.Medicinal research reviews · 2020Review
- The Parkinson's disease gene product DJ-1 modulates miR-221 to promote neuronal survival against oxidative stress.Redox biology · 2018Article
- Role of Mitogen Activated Protein Kinase Signaling in Parkinson's Disease.International journal of molecular sciences · 2018Review
- Interaction of DJ-1 with Lyn is essential for IgE-mediated stimulation of human mast cells.The Journal of allergy and clinical immunology · 2018Article
- Cytoprotective mechanisms of DJ-1 against oxidative stress through modulating ERK1/2 and ASK1 signal transduction.Redox biology · 2018Review
- Anti-TNF-alpha antibody attenuates subarachnoid hemorrhage-induced apoptosis in the hypothalamus by inhibiting the activation of Erk.Neuropsychiatric disease and treatment · 2018Article
- Regulation of Signal Transduction by DJ-1.Advances in experimental medicine and biology · 2017Article
- The Ras/Raf/Erk Pathway Mediates the Subarachnoid Hemorrhage-Induced Apoptosis of Hippocampal Neurons Through Phosphorylation of p53.Molecular neurobiology · 2016Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DJ-1 is an oncogene and also a causative gene for familial Parkinson disease. DJ-1 has various functions, and the oxidative status of cysteine at position 106 (Cys-106) is crucial for determination of the activation level of DJ-1. Although DJ-1 requires activated Ras for its oncogenic activity and although it activates the extracellular signal-regulated kinase (ERK) pathway, a cell growth pathway downstream of Ras, the precise mechanism underlying activation of the ERK pathway by DJ-1 is still not known. In this study, we found that DJ-1 directly bound to the kinase domain of c-Raf but not to Ras and that Cys-106 mutant DJ-1 bound to c-Raf more weakly than did wild-type DJ-1. Co-localization of DJ-1 with c-Raf in the cytoplasm was enhanced in epidermal growth factor (EGF)-treated cells. Knockdown of DJ-1 expression attenuated the phosphorylation level of c-Raf in EGF-treated cells, resulting in reduced activation of MEK and ERK1/2. Although EGF-treated DJ-1 knock-out cells also showed attenuated c-Raf activation, reintroduction of wild-type DJ-1, but not C106S DJ-1, into DJ-1 knock-out cells restored c-Raf activation in a DJ-1 binding activity in a c-Raf-dependent manner. DJ-1 was not responsible for activation of c-Raf in phorbol myristate acetate-treated cells. Furthermore, DJ-1 stimulated self-phosphorylation activity of c-Raf in vitro, but DJ-1 was not a target for Raf kinase. Oxidation of Cys-106 in DJ-1 was not affected by EGF treatment. These findings showed that DJ-1 is a positive regulator of the EGF/Ras/ERK pathway through targeting c-Raf.
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