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Reelin signals survival through Src‐family kinases that inactivate BAD activity
Author(s) -
Ohkubo Nobutaka,
Vitek Michael P.,
Morishima Atsuyuki,
Suzuki Yoji,
Miki Tetsuro,
Maeda Nobuji,
Mitsuda Noriaki
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04804.x
Subject(s) - reelin , dab1 , phosphorylation , protein kinase b , microbiology and biotechnology , retinoic acid , kinase , signal transduction , pi3k/akt/mtor pathway , biology , cancer research , chemistry , biochemistry , gene , extracellular matrix
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.