PMID- 10320030 OWN - NLM STAT- MEDLINE DCOM- 19990617 LR - 20220331 IS - 0304-3940 (Print) IS - 0304-3940 (Linking) VI - 264 IP - 1-3 DP - 1999 Apr 2 TI - Sustained phosphorylation and activation of protein kinase B correlates with brain-derived neurotrophic factor and insulin stimulated survival of cerebellar granule cells. PG - 125-8 AB - 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. FAU - Foulstone, E J AU - Foulstone EJ AD - Department of Biochemistry, School of Medical Sciences, University of Bristol, UK. FAU - Tavare, J M AU - Tavare JM FAU - Gunn-Moore, F J AU - Gunn-Moore FJ LA - eng PT - Journal Article PL - Ireland TA - Neurosci Lett JT - Neuroscience letters JID - 7600130 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Insulin) RN - 0 (Proto-Oncogene Proteins) RN - 62229-50-9 (Epidermal Growth Factor) RN - EC 2.7.11.- (Glycogen Synthase Kinases) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases) RN - EC 2.7.11.26 (Glycogen Synthase Kinase 3) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Calcium-Calmodulin-Dependent Protein Kinases/metabolism MH - Cell Survival/drug effects MH - Cerebellum/cytology/*drug effects/*enzymology MH - Enzyme Activation/physiology MH - Epidermal Growth Factor/pharmacology MH - Glycogen Synthase Kinase 3 MH - Glycogen Synthase Kinases MH - Insulin/*pharmacology MH - Neurons/*enzymology MH - *Protein Serine-Threonine Kinases MH - Proto-Oncogene Proteins/*metabolism MH - Proto-Oncogene Proteins c-akt MH - Rats MH - Time Factors EDAT- 1999/05/13 00:00 MHDA- 1999/05/13 00:01 CRDT- 1999/05/13 00:00 PHST- 1999/05/13 00:00 [pubmed] PHST- 1999/05/13 00:01 [medline] PHST- 1999/05/13 00:00 [entrez] AID - S0304-3940(99)00166-4 [pii] AID - 10.1016/s0304-3940(99)00166-4 [doi] PST - ppublish SO - Neurosci Lett. 1999 Apr 2;264(1-3):125-8. doi: 10.1016/s0304-3940(99)00166-4.