Analysis of Ret knockin mice reveals a critical role for IKKs, but not PI 3-K, in neurotrophic factor-induced survival of sympathetic neurons
| العنوان: | Analysis of Ret knockin mice reveals a critical role for IKKs, but not PI 3-K, in neurotrophic factor-induced survival of sympathetic neurons |
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| المؤلفون: | Joan X. Comella, Sanjay Jain, Esteban J. Rozen, Xavier Dolcet, Jeffrey Milbrandt, Eugene M. Johnson, Mario Encinas |
| المصدر: | Recercat. Dipósit de la Recerca de Catalunya instname Repositorio Abierto de la UdL Universitad de Lleida |
| بيانات النشر: | Nature Publishing Group |
| مصطلحات موضوعية: | Proto-Oncogene Proteins B-raf, Sympathetic Nervous System, Cell Survival, Article, Mice, Phosphatidylinositol 3-Kinases, Neurotrophic factors, Nerve Growth Factor, Glial cell line-derived neurotrophic factor, Animals, Humans, Glial Cell Line-Derived Neurotrophic Factor, Tyrosine, Extracellular Signal-Regulated MAP Kinases, Molecular Biology, PI3K/AKT/mTOR pathway, Cells, Cultured, Cell Size, Neurons, Gene knockdown, biology, Proto-Oncogene Proteins c-ret, Sistema nerviós--Malalties, Cell Biology, Molecular biology, Mice, Mutant Strains, Cell biology, I-kappa B Kinase, enzymes and coenzymes (carbohydrates), Nerve growth factor, nervous system, Mutation, biology.protein, Signal transduction, Proto-Oncogene Proteins c-akt, Signal Transduction |
| الوصف: | We analyzed the survival responses and downstream signaling elicited by GDNF on sympathetic neurons from different Ret knockin mice. Lack of tyrosine 1062, a multidocking site in Ret, completely prevented GDNF-mediated survival. Importantly lack of tyrosine 981, although abrogating Akt phosphorylation, had no effect on neuronal survival, indicating that the PI 3-K/Akt pathway is not necessary for survival of sympathetic neurons. In contrast, silencing of B-Raf completely prevented not only GDNF-mediated but also NGF-mediated cell survival, independently of MEK-1/2. We identified IKKs as the main effectors of the protective effects of B-Raf. First, BRaf interacted with and activated IKKs. Second, knockdown of IKKs reversed the protection afforded by a constitutively active form of B-Raf. Third, knockdown of IKKs prevented both NGF- and GDNF-mediated survival. In conclusion, our data delineate a novel survival pathway for sympathetic neurons linking B-Raf to IKKs, independently of both PI 3-K and MEK-1/2 pathways. |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a99a89db96214e67b397e51200325ff2 http://hdl.handle.net/10459.1/47782 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....a99a89db96214e67b397e51200325ff2 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |