ArticleScientific reports2016
cJun N-terminal kinase (JNK) phosphorylation of serine 36 is critical for p66Shc activation.
Article in Scientific reports, 2016. 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, 37 citations in OpenAlex.
- Exploiting metabolic adaptations to overcome dabrafenib treatment resistance in melanoma cells.Molecular oncology · 2026Article
- Article
- Overcoming β-Cell Dysfunction in Type 2 Diabetes Mellitus: CD36 Inhibition and Antioxidant System.Diabetes & metabolism journal · 2025Review
- Lysosomal damage triggers a p38 MAPK-dependent phosphorylation cascade to promote lysophagy via the small heat shock protein HSP27.Current biology : CB · 2024Article
- Relevance of the endoplasmic reticulum-mitochondria axis in cancer diagnosis and therapy.Experimental & molecular medicine · 2024Review
- Cardioprotective Effects of a Selective c-Jun N-terminal Kinase Inhibitor in a Rat Model of Myocardial Infarction.Biomedicines · 2023Article
- Aberrant activation of p53/p66Shc-mInsc axis increases asymmetric divisions and attenuates proliferation of aged mammary stem cells.Cell death and differentiation · 2022Article
- Ferroptosis Signaling in Pancreatic β-Cells: Novel Insights & Therapeutic Targeting.International journal of molecular sciences · 2022Review
- The role of mitochondria-associated membranes mediated ROS on NLRP3 inflammasome in cardiovascular diseases.Frontiers in cardiovascular medicine · 2022Review
- CD36 Signal Transduction in Metabolic Diseases: Novel Insights and Therapeutic Targeting.Cells · 2021Review
- NADPH Oxidase (NOX) Targeting in Diabetes: A Special Emphasis on Pancreatic β-Cell Dysfunction.Cells · 2021Review
- Mitochondrial Fission Protein 1: Emerging Roles in Organellar Form and Function in Health and Disease.Frontiers in endocrinology · 2021Review
- Electro-Acupuncture Inhibits p66Shc-Mediated Oxidative Stress to Facilitate Functional Recovery After Spinal Cord Injury.Journal of molecular neuroscience : MN · 2020Article
- Reactive oxygen species (ROS) generation as an underlying mechanism of inorganic phosphate (PFree radical biology & medicine · 2020Article
- Article
- The Role of CD36 in Type 2 Diabetes Mellitus: β-Cell Dysfunction and Beyond.Diabetes & metabolism journal · 2020Review
- JNK/p66Shc/ITCH Signaling Pathway Mediates Angiotensin II-induced Ferritin Degradation and Labile Iron Pool Increase.Nutrients · 2020Article
- Arrestin-3 scaffolding of the JNK3 cascade suggests a mechanism for signal amplification.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- The oxidoreductase p66Shc acts as tumor suppressor in BRAFV600E-transformed cells.Molecular oncology · 2018Article
- c-Jun N-Terminal Kinases (JNKs) in Myocardial and Cerebral Ischemia/Reperfusion Injury.Frontiers in pharmacology · 2018Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
p66Shc-dependent ROS production contributes to many pathologies including ischemia/reperfusion injury (IRI) during solid organ transplantation. Inhibiting p66Shc activation may provide a novel therapeutic approach to prevent damage, which is poorly managed by antioxidants in vivo. Previous work suggested that pro-oxidant and a pro-apoptotic function of p66Shc required mitochondrial import, which depended on serine 36 phosphorylation. PKCß has been proposed as S36 kinase but cJun N-terminal kinases (JNKs) may also phosphorylate this residue. To simulate the early stages of ischemia/reperfusion (IR) we either used H2O2 treatment or hypoxia/reoxygenation (HR). As during reperfusion in vivo, we observed increased JNK and p38 activity in mouse embryonic fibroblasts (MEFs) and HL-1 cardiomyocytes along with significantly increased p66ShcS36 phosphorylation, ROS production and cell damage. Application of specific inhibitors caused a pronounced decrease in p66ShcS36 phosphorylation only in the case of JNK1/2. Moreover, S36 phosphorylation of recombinant p66Shc by JNK1 but not PKCß was demonstrated. We further confirmed JNK1/2-dependent regulation of p66ShcS36 phosphorylation, ROS production and cell death using JNK1/2 deficient MEFs. Finally, the low ROS phenotype of JNK1/2 knockout MEFs was reversed by the phosphomimetic p66ShcS36E mutant. Inhibiting JNK1/2-regulated p66Shc activation may thus provide a therapeutic approach for the prevention of oxidative damage.
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