Sustained phosphorylation and activation of protein kinase B correlates with brain-derived neurotrophic factor and insulin stimulated survival of cerebellar granule cells.

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.

journal_name

Neurosci Lett

journal_title

Neuroscience letters

authors

Foulstone EJ,Tavaré JM,Gunn-Moore FJ

doi

10.1016/s0304-3940(99)00166-4

keywords:

subject

Has Abstract

pub_date

1999-04-02 00:00:00

pages

125-8

issue

1-3

eissn

0304-3940

issn

1872-7972

pii

S0304-3940(99)00166-4

journal_volume

264

pub_type

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