| 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
|
| 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
|
| Times Cited |
21
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
NEUROSCIENCES
|
| Resource |
| Human and Animal Cells |
|
