Reelin signals survival through Src-family kinases that inactivate BAD activity

Autor:	Nobutaka Ohkubo, Tetsuro Miki, Atsuyuki Morishima, Yoji Suzuki, Noriaki Mitsuda, Nobuji Maeda, Michael P. Vitek
Rok vydání:	2007
Předmět:	biology Kinase Retinoic acid DAB1 Biochemistry Cellular and Molecular Neuroscience chemistry.chemical_compound nervous system chemistry biology.protein Cancer research Phosphorylation Reelin Signal transduction Protein kinase B PI3K/AKT/mTOR pathway
Zdroj:	Journal of Neurochemistry. 103:820-830
ISSN:	0022-3042
DOI:	10.1111/j.1471-4159.2007.04804.x
Popis:	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.
Databáze:	OpenAIRE
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