RRC ID 43079
Author Ohkubo N, Vitek MP, Morishima A, Suzuki Y, Miki T, Maeda N, Mitsuda N.
Title Reelin signals survival through Src-family kinases that inactivate BAD activity.
Journal 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.
Volume 103(2)
Pages 820-30
Published 2007-10-1
DOI 10.1111/j.1471-4159.2007.04804.x
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
Times Cited 21
Human and Animal Cells