ArticlePloS one2012
JNK3 maintains expression of the insulin receptor substrate 2 (IRS2) in insulin-secreting cells: functional consequences for insulin signaling.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- Insulin receptor substrate 2 (IRS2) confers resistance to PI3K pathway inhibition in PIK3CA mutant breast cancer.The Journal of biological chemistry · 2026Article
- JNK3 regulates β cell responses to incretins in human islets and mouse models.The Journal of clinical investigation · 2026Article
- Alpha-ketoglutarate mitigates insulin resistance and metabolic inflexibility in a mouse model of Ataxia-Telangiectasia.Nature communications · 2025Article
- Genetic deletion of c-Jun amino-terminal kinase 3 (JNK3) modestly increases disease severity in a mouse model of multiple sclerosis.Journal of neuroimmunology · 2023Article
- Inhibition of the type 1 diabetes candidate gene PTPN2 aggravates TNF-α-induced human beta cell dysfunction and death.Diabetologia · 2023Article
- Novel Tryptanthrin Derivatives with Selectivity asMolecules (Basel, Switzerland) · 2023Article
- Impact of Conventional and Atypical MAPKs on the Development of Metabolic Diseases.Biomolecules · 2020Review
- Review
- Review
- C-Jun N-terminal kinase inhibitors: Structural insight into kinase-inhibitor complexes.Computational and structural biotechnology journal · 2020Review
- JNK at the crossroad of obesity, insulin resistance, and cell stress response.Molecular metabolism · 2017Review
- Protein kinases: mechanisms and downstream targets in inflammation-mediated obesity and insulin resistance.Molecular and cellular biochemistry · 2017Review
- Proteasome inhibitors, including curcumin, improve pancreatic β-cell function and insulin sensitivity in diabetic mice.Nutrition & diabetes · 2016Article
- A20 Inhibits β-Cell Apoptosis by Multiple Mechanisms and Predicts Residual β-Cell Function in Type 1 Diabetes.Molecular endocrinology (Baltimore, Md.) · 2016Article
- JNK1 Deficient Insulin-Producing Cells Are Protected against Interleukin-1β-Induced Apoptosis Associated with Abrogated Myc Expression.Journal of diabetes research · 2016Article
- Variations in Glycogen Synthesis in Human Pluripotent Stem Cells with Altered Pluripotent States.PloS one · 2015Article
- JNK3 is required for the cytoprotective effect of exendin 4.Journal of diabetes research · 2014Article
- Regulation of the JNK3 signaling pathway during islet isolation: JNK3 and c-fos as new markers of islet quality for transplantation.PloS one · 2014Article
- c-Jun N-Terminal Kinases Mediate a Wide Range of Targets in the Metastatic Cascade.Genes & cancer · 2013Review
- JNK1/2 regulates ER-mitochondrial Ca2+ cross-talk during IL-1β-mediated cell death in RINm5F and human primary β-cells.Molecular biology of the cell · 2013Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have recently shown that silencing of the brain/islet specific c-Jun N-terminal Kinase3 (JNK3) isoform enhances both basal and cytokine-induced beta-cell apoptosis, whereas silencing of JNK1 or JNK2 has opposite effects. While it is known that JNK1 or JNK2 may promote apoptosis by inhibiting the activity of the pro-survival Akt pathway, the effect of JNK3 on Akt has not been documented. This study aims to determine the involvement of individual JNKs and specifically JNK3 in the regulation of the Akt signaling pathway in insulin-secreting cells. JNK3 silencing strongly decreases Insulin Receptor Substrate 2 (IRS2) protein expression, and blocks Akt2 but not Akt1 activation by insulin, while the silencing of JNK1 or JNK2 activates both Akt1 and Akt2. Concomitantly, the silencing of JNK1 or JNK2, but not of JNK3, potently phosphorylates the glycogen synthase kinase3 (GSK3β). JNK3 silencing also decreases the activity of the transcription factor Forkhead BoxO3A (FoxO3A) that is known to control IRS2 expression, in addition to increasing c-Jun levels that are known to inhibit insulin gene expression. In conclusion, we propose that JNK1/2 on one hand and JNK3 on the other hand, have opposite effects on insulin-signaling in insulin-secreting cells; JNK3 protects beta-cells from apoptosis and dysfunction mainly through maintenance of a normal IRS2 to Akt2 signaling pathway. It seems that JNK3 mediates its effects mainly at the transcriptional level, while JNK1 or JNK2 appear to mediate their pro-apoptotic effect in the cytoplasm.
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