PMID- 16171514
OWN - NLM
STAT- MEDLINE
DCOM- 20060207
LR  - 20211203
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 95
IP  - 5
DP  - 2005 Dec
TI  - Enhancement of translation elongation in neurons by brain-derived neurotrophic 
      factor: implications for mammalian target of rapamycin signaling.
PG  - 1438-45
AB  - The effects and signaling mechanisms of brain-derived neurotrophic factor (BDNF) 
      on translation elongation were investigated in cortical neurons. BDNF increased 
      the elongation rate approximately twofold, as determined by measuring the 
      ribosomal transit time. BDNF-accelerated elongation was inhibited by rapamycin, 
      implicating the mammalian target of rapamycin (mTOR). To explore the mechanisms 
      underlying these effects, we examined the protein phosphorylation cascades that 
      lead to the activation of translation elongation in neurons. BDNF increased 
      eukaryote elongation factor 1A (eEF1A) phosphorylation and decreased eEF2 
      phosphorylation. Whereas eEF2 phosphorylation levels altered by BDNF were 
      inhibited by rapamycin, eEF1A phosphorylation was not affected by rapamycin or 
      PD98059, a mitogen-activated protein kinase kinase (MEK) inhibitor. BDNF induced 
      phosphorylation of eEF2 kinase (Ser366), as well as decreased its kinase 
      activity. All these events were inhibited by rapamycin. Furthermore, mTOR siRNA, 
      which reduced mTOR levels up to 50%, inhibited the BDNF-induced enhancement in 
      elongation rate and decrease in eEF2 phosphorylation. These results strongly 
      suggest that BDNF enhances translation elongation through the activation of the 
      mTOR-eEF2 pathway.
FAU - Inamura, Naoko
AU  - Inamura N
AD  - Department of Molecular Neurobiology, Brain Research Institute, Niigata 
      University, Niigata, Japan.
FAU - Nawa, Hiroyuki
AU  - Nawa H
FAU - Takei, Nobuyuki
AU  - Takei N
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050920
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Flavonoids)
RN  - 0 (MAP2 protein, rat)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Peptide Elongation Factor 1)
RN  - 0 (Phosphorus Isotopes)
RN  - 0 (RNA, Double-Stranded)
RN  - 2ZD004190S (Threonine)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.1.17 (Eef2k protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.20 (Elongation Factor 2 Kinase)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Blotting, Western/methods
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Calcium-Calmodulin-Dependent Protein Kinases/immunology
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology
MH  - Drug Interactions
MH  - Elongation Factor 2 Kinase
MH  - Flavonoids/pharmacology
MH  - Gene Expression Regulation/drug effects/physiology
MH  - Immunohistochemistry/methods
MH  - Microtubule-Associated Proteins/metabolism
MH  - Neurons/*drug effects
MH  - Peptide Elongation Factor 1/metabolism
MH  - Phosphorus Isotopes/metabolism
MH  - Phosphorylation/drug effects
MH  - Protein Biosynthesis/*drug effects/physiology
MH  - Protein Kinases/metabolism
MH  - RNA, Double-Stranded/pharmacology
MH  - Rats
MH  - Ribosomes/metabolism
MH  - Signal Transduction/*drug effects/physiology
MH  - Sirolimus/*pharmacology
MH  - TOR Serine-Threonine Kinases
MH  - Threonine/metabolism
MH  - Time Factors
EDAT- 2005/09/21 09:00
MHDA- 2006/02/08 09:00
CRDT- 2005/09/21 09:00
PHST- 2005/09/21 09:00 [pubmed]
PHST- 2006/02/08 09:00 [medline]
PHST- 2005/09/21 09:00 [entrez]
AID - JNC3466 [pii]
AID - 10.1111/j.1471-4159.2005.03466.x [doi]
PST - ppublish
SO  - J Neurochem. 2005 Dec;95(5):1438-45. doi: 10.1111/j.1471-4159.2005.03466.x. Epub 
      2005 Sep 20.