論文 - 詳細
| RRC ID | 43079 |
|---|---|
| 著者 | Ohkubo N, Vitek MP, Morishima A, Suzuki Y, Miki T, Maeda N, Mitsuda N. |
| タイトル | Reelin signals survival through Src-family kinases that inactivate BAD activity. |
| ジャーナル | J Neurochem |
| Abstract |
Reelin plays an important role in the migration of embryonic neurons, but its continuing presence suggests additional functions in the brain. We now report a novel function where reelin protects P19 embryonal cells from apoptosis during retinoic acid-induced neuronal differentiation. This increased survival is associated with reelin activation of the phosphatidyl-inositol-3-kinase (PI3 K)/Akt pathway. When PI3 K was inhibited with LY294002, reelin failed to protect against this retinoic acid-induced apoptosis. The protective effect of reelin includes activating the Src-family kinases/PI3 K/Akt pathway which then led to selective phosphorylation of Bcl-2/Bcl-XL associated death promoter (BAD) at serine-136, while the phosphorylation-incompetent mutation of BAD (S136A) suppressed this protection. These and additional studies define a novel pathway where reelin binds apoE receptors, significantly activates the PI3 K/Akt pathway causing phosphorylation of BAD which helps to protect cells from apoptosing, thus serving an important role in promoting the survival of maturing neurons in the brain. |
| 巻・号 | 103(2) |
| ページ | 820-30 |
| 公開日 | 2007-10-1 |
| DOI | 10.1111/j.1471-4159.2007.04804.x |
| PII | JNC4804 |
| PMID | 17696989 |
| MeSH | Animals Blotting, Western Cell Adhesion Molecules, Neuronal / antagonists & inhibitors Cell Adhesion Molecules, Neuronal / physiology* Cell Line Cell Survival / physiology Extracellular Matrix Proteins / antagonists & inhibitors Extracellular Matrix Proteins / physiology* Glycogen Synthase Kinase 3 / metabolism Glycogen Synthase Kinase 3 beta HeLa Cells Humans Mutation Nerve Tissue Proteins / antagonists & inhibitors Nerve Tissue Proteins / physiology* Neurons / physiology* Oncogene Protein v-akt / physiology Phosphoinositide-3 Kinase Inhibitors Phosphorylation Reelin Protein Serine Endopeptidases / physiology* Signal Transduction / physiology* Stem Cells / physiology Transfection Tretinoin / pharmacology bcl-Associated Death Protein / genetics bcl-Associated Death Protein / physiology* raf Kinases / metabolism src-Family Kinases / physiology* |
| IF | 4.066 |
| 引用数 | 21 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY NEUROSCIENCES |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | P19 |