Sustained phosphorylation and activation of protein kinase B correlates with brain-derived neurotrophic factor and insulin stimulated survival of cerebellar granule cells.
Neurosci Lett
; 264(1-3): 125-8, 1999 Apr 02.
Article
em En
| MEDLINE
| ID: mdl-10320030
ABSTRACT
Brain-derived neurotrophic factor (BDNF) and insulin promote the survival of 6-7 day old post-natal rat cerebellar granule cells. Previous studies using the PI3 kinase inhibitor, wortmannin and the over-expression of protein kinase B (PKB) have indicated that both PI3 kinase and PKB activation are central for insulin-stimulated survival of these neurones. Here we report that BDNF, insulin and epidermal growth factor (EGF) all cause the phosphorylation and stimulation of endogenous PKB activity, though with differing profiles. The addition of BDNF, or insulin resulted in a rapid and sustained phosphorylation and stimulation of PKB activity, whilst EGF stimulation, which does not promote survival, caused a more transient phosphorylation and stimulation of PKB activity. We also investigated the involvement of the PKB substrate, glycogen synthase kinase 3 (GSK 3). All three growth factors caused the inactivation of GSK-3beta, suggesting that the inactivation of GSK-3beta does not correlate with survival.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cerebelo
/
Proteínas Proto-Oncogênicas
/
Proteínas Serina-Treonina Quinases
/
Fator Neurotrófico Derivado do Encéfalo
/
Insulina
/
Neurônios
Limite:
Animals
Idioma:
En
Revista:
Neurosci Lett
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Reino Unido