PMID- 11551908
OWN - NLM
STAT- MEDLINE
DCOM- 20011226
LR  - 20240109
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 276
IP  - 46
DP  - 2001 Nov 16
TI  - Brain-derived neurotrophic factor enhances neuronal translation by activating 
      multiple initiation processes: comparison with the effects of insulin.
PG  - 42818-25
AB  - The effects of neurotrophic factors on translational activation were investigated 
      in cortical neurons. Brain-derived neurotrophic factor (BDNF) increased protein 
      synthesis within 30 min, whereas insulin produced a weaker enhancement of protein 
      synthesis. BDNF-triggered protein synthesis was inhibited by LY294002, PD98059, 
      and rapamycin, whereas the effect of insulin was unaffected by PD98059. To 
      explore the mechanisms underlying this effect, the protein phosphorylation 
      cascades that lead to the activation of translation initiation in neurons were 
      examined. BDNF induced the phosphorylation of both eukaryote initiation factor 
      (eIF) 4E and its binding protein (eIF4E-binding protein-1). The former reaction 
      was inhibited by PD98059, whereas the latter was inhibited by LY294002 or 
      rapamycin. In agreement, BDNF induced the phosphorylation of mammalian TOR 
      (target of rapamycin) and enhanced its kinase activity toward eIF4E-binding 
      protein-1. In contrast, insulin failed to activate MAPK and did not induce the 
      phosphorylation of eIF4E. Since BDNF and insulin increased the activity of eIF2B 
      and eIF2, the only difference between them was eIF4E phosphorylation. Thus, this 
      may explain the lower activity of insulin in potentiating neuronal protein 
      synthesis. These results suggest strongly that BDNF simultaneously activates 
      multiple signaling cascades consisting of phosphatidylinositol 3-kinase, 
      mammalian TOR, and MAPK to enhance translation initiation in neurons.
FAU - Takei, N
AU  - Takei N
AD  - Department of Molecular Neurobiology, Brain Research Institute, Niigata 
      University, Asahimachi 1, Niigata 951-8585, Japan. nobtak@bri.niigata-u.ac.jp
FAU - Kawamura, M
AU  - Kawamura M
FAU - Hara, K
AU  - Hara K
FAU - Yonezawa, K
AU  - Yonezawa K
FAU - Nawa, H
AU  - Nawa H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20010910
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Chromones)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Eukaryotic Initiation Factor-4E)
RN  - 0 (Flavonoids)
RN  - 0 (Insulin)
RN  - 0 (Morpholines)
RN  - 0 (Peptide Initiation Factors)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - AE28F7PNPL (Methionine)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Anti-Bacterial Agents/pharmacology
MH  - Blotting, Western
MH  - Brain/cytology/*drug effects/embryology
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cells, Cultured
MH  - Chromones/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/pharmacology
MH  - Eukaryotic Initiation Factor-4E
MH  - Flavonoids/pharmacology
MH  - Insulin/*pharmacology
MH  - MAP Kinase Signaling System
MH  - Methionine/pharmacology
MH  - Morpholines/pharmacology
MH  - Neurons/*metabolism
MH  - Peptide Initiation Factors/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation
MH  - Protein Binding
MH  - *Protein Biosynthesis
MH  - Rats
MH  - Signal Transduction
MH  - Sirolimus/pharmacology
MH  - Time Factors
MH  - Up-Regulation
EDAT- 2001/09/12 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/09/12 10:00
PHST- 2001/09/12 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/09/12 10:00 [entrez]
AID - S0021-9258(19)82906-X [pii]
AID - 10.1074/jbc.M103237200 [doi]
PST - ppublish
SO  - J Biol Chem. 2001 Nov 16;276(46):42818-25. doi: 10.1074/jbc.M103237200. Epub 2001 
      Sep 10.