PMID- 12373512
OWN - NLM
STAT- MEDLINE
DCOM- 20040226
LR  - 20211203
IS  - 0939-4451 (Print)
IS  - 0939-4451 (Linking)
VI  - 23
IP  - 1-3
DP  - 2002
TI  - Co-activation of the phosphatidylinositol-3-kinase/Akt signaling pathway by 
      N-methyl-D-aspartate and TrkB receptors in cerebellar granule cell neurons.
PG  - 11-7
AB  - Neuroprotective concentrations of N-methyl-D-aspartate (NMDA) promote survival of 
      cerebellar granule cell neurons against glutamate excitotoxicity through a TrkB 
      receptor-mediated brain-derived neurotrophic factor (BDNF) autocrine loop. 
      However, the intracellular signaling pathway(s) are not clear. Our results show 
      that PI-3 kinase/Akt is activated by either NMDA or BDNF displaying differential 
      kinetics. BDNF and NMDA increased Akt phosphorylation within 5 minutes but 
      maximal activation by NMDA was observed at 3 hours. Akt phosphorylation was 
      completely blocked by the PI-3 kinase inhibitor LY294002. NMDA-mediated 
      activation of Akt was completely blocked by MK-801 and partially blocked by the 
      TrkB receptor inhibitor, K252a, indicating the requirement of TrkB receptors for 
      maximal activation by NMDA. In contrast, BDNF-induced Akt phosphorylation was 
      abolished by K252a, but not by the addition of MK-801. Therefore, the PI-3 
      kinase/Akt pathway is co-activated by NMDA and TrkB receptors. The kinetics of 
      BDNF and NMDA-mediated activation of PI-3 kinase/Akt suggests that they have 
      different roles in intraneuronal time-related events.
FAU - Zhu, D
AU  - Zhu D
AD  - Department of Neurology and Neuroscience, Uniformed Services University of the 
      Health Sciences, Bethesda, Maryland 20814, USA.
FAU - Lipsky, R H
AU  - Lipsky RH
FAU - Marini, A M
AU  - Marini AM
LA  - eng
PT  - Journal Article
PL  - Austria
TA  - Amino Acids
JT  - Amino acids
JID - 9200312
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Carbazoles)
RN  - 0 (Chromones)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Indole Alkaloids)
RN  - 0 (Morpholines)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - 97161-97-2 (staurosporine aglycone)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.11.1 (Akt1 protein, rat)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Carbazoles/metabolism
MH  - Cells, Cultured
MH  - Cerebellum/*cytology/metabolism
MH  - Chromones/metabolism
MH  - Dizocilpine Maleate/metabolism
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/metabolism
MH  - Excitatory Amino Acid Agonists/metabolism
MH  - Excitatory Amino Acid Antagonists/metabolism
MH  - Indole Alkaloids
MH  - Morpholines/metabolism
MH  - N-Methylaspartate/metabolism
MH  - Neurons/cytology/*metabolism
MH  - Neuroprotective Agents/metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - *Protein Serine-Threonine Kinases
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/*metabolism
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Signal Transduction/*physiology
EDAT- 2002/10/10 04:00
MHDA- 2004/02/27 05:00
CRDT- 2002/10/10 04:00
PHST- 2002/10/10 04:00 [pubmed]
PHST- 2004/02/27 05:00 [medline]
PHST- 2002/10/10 04:00 [entrez]
AID - 10.1007/s00726-001-0103-9 [doi]
PST - ppublish
SO  - Amino Acids. 2002;23(1-3):11-7. doi: 10.1007/s00726-001-0103-9.