GSK-3β acts downstream of PP2A and the PI 3-kinase-Akt pathway, and upstream of caspase-2 in ceramide-induced mitochondrial apoptosis
| العنوان: | GSK-3β acts downstream of PP2A and the PI 3-kinase-Akt pathway, and upstream of caspase-2 in ceramide-induced mitochondrial apoptosis |
|---|---|
| المؤلفون: | Yee Shin Lin, Chi Wu Chiang, Wei Ching Huang, Chiou Feng Lin, Chia Ling Chen, Ming-Shiou Jan |
| المصدر: | Journal of Cell Science. 120:2935-2943 |
| بيانات النشر: | The Company of Biologists, 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Ceramide, Small interfering RNA, Caspase 2, Apoptosis, macromolecular substances, Ceramides, Models, Biological, Glycogen Synthase Kinase 3, Mice, Phosphatidylinositol 3-Kinases, chemistry.chemical_compound, Cell Line, Tumor, Animals, Humans, Protein Phosphatase 2, Enzyme Inhibitors, Glycogen synthase, GSK3B, PI3K/AKT/mTOR pathway, Caspase 8, Glycogen Synthase Kinase 3 beta, biology, Cell Biology, Protein phosphatase 2, Molecular biology, Mitochondria, Cell biology, Enzyme Activation, chemistry, biology.protein, Proto-Oncogene Proteins c-akt, BH3 Interacting Domain Death Agonist Protein, Signal Transduction |
| الوصف: | The signaling of glycogen synthase kinase-3beta (GSK-3beta) has been implicated in stress-induced apoptosis. However, the pro-apoptotic role of GSK-3beta is still unclear. Here, we show the involvement of GSK-3beta in ceramide-induced mitochondrial apoptosis. Ceramide induced GSK-3beta activation via protein dephosphorylation at serine 9. We previously reported that ceramide induced caspase-2 and caspase-8 activation, Bid cleavage, mitochondrial damage, and apoptosis. In this study, we found that caspase-2 activation and the subsequent apoptotic events were abolished by the GSK-3beta inhibitors lithium chloride and SB216763, and by GSK-3beta knockdown using short interfering RNA. We also found that ceramide-activated protein phosphatase 2A (PP2A) indirectly caused GSK-3beta activation, and that the PP2A-regulated PI 3-kinase-Akt pathway was involved in GSK-3beta activation. These results indicate a role for GSK-3beta in ceramide-induced apoptosis, in which GSK-3beta acts downstream of PP2A and the PI 3-kinase-Akt pathway, and upstream of caspase-2 and caspase-8. |
| تدمد: | 1477-9137 0021-9533 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d00db4401e4fa15d0c418bc150c57e20Test https://doi.org/10.1242/jcs.03473Test |
| رقم الانضمام: | edsair.doi.dedup.....d00db4401e4fa15d0c418bc150c57e20 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14779137 00219533 |
|---|