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
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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
|
リソース情報 |
ヒト・動物細胞 |
|