PMID- 12699783
OWN - NLM
STAT- MEDLINE
DCOM- 20030616
LR  - 20211203
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 118
IP  - 2
DP  - 2003
TI  - A calcium/calmodulin kinase pathway connects brain-derived neurotrophic factor to 
      the cyclic AMP-responsive transcription factor in the rat hippocampus.
PG  - 477-90
AB  - Brain-derived neurotrophic factor (BDNF) plays fundamental roles in synaptic 
      plasticity in rat hippocampus. Recently, using rat hippocampal slices, we found 
      that BDNF induces activation of calcium/calmodulin-dependent protein kinase 2 
      (CaMKII), a critical mediator of synaptic plasticity. CaMKII in turn activates 
      the p38 subfamily of mitogen-activated protein kinases (MAPK) and its downstream 
      effector, MAPK-activated protein kinase 2 (MAPKAPK-2). Herein, we determined 
      whether some kinases of this pathway connect BDNF to the cyclic AMP response 
      element -binding protein (CREB), a transcription factor also involved in 
      plasticity and survival. Crude cytosolic and nuclear fractions were prepared from 
      hippocampal slices of adult rat, and then kinase involvement in CREB 
      phosphorylation was studied with a combination of pharmacologic inhibition and 
      antibody depletion. In addition, the regional localization of this signaling 
      pathway was immunohistochemically investigated. We show that: (i). the 
      BDNF-stimulated CaMKII cascade phosphorylates the key positive regulatory site of 
      CREB via its end MAPKAPK-2 component; (ii). this process appears to be highly 
      localized in the outermost cell layer of the dentate gyrus. The present findings 
      suggest that CaMKII is involved in neurotrophic-dependent activation of CREB in 
      the dentate gyrus. Such a signaling process could be important for controlling 
      synaptic plasticity in this major area for the afferent inputs to the hippocampal 
      formation.
FAU - Blanquet, P R
AU  - Blanquet PR
AD  - Laboratoire Developpement et Vieillissement du Systeme Nerveux UMR 7102 CNRS-UPMC 
      (Neurobiologie des Processus Adaptatifs), Universite P & M Curie, 9 Quai 
      Saint-Bernard, Batiment B, 4e Etage, Boite 14, 75005 Paris, France. 
      pierre.blanquet@snv.jussieu.fr
FAU - Mariani, J
AU  - Mariani J
FAU - Derer, P
AU  - Derer P
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (AG-879)
RN  - 0 (Acetophenones)
RN  - 0 (Alkaloids)
RN  - 0 (Androstadienes)
RN  - 0 (Antibodies)
RN  - 0 (Benzophenanthridines)
RN  - 0 (Benzopyrans)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Calmodulin)
RN  - 0 (Carbazoles)
RN  - 0 (Chromones)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Imidazoles)
RN  - 0 (Indoles)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Morpholines)
RN  - 0 (Naphthalenes)
RN  - 0 (Phenanthridines)
RN  - 0 (Pyridines)
RN  - 0 (Pyrroles)
RN  - 0 (Tyrphostins)
RN  - 0 (calphostin complex)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - 58HV29I28S (KT 5720)
RN  - 63HM46XPOW (KN 62)
RN  - 84477-87-2 (1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine)
RN  - E29LP3ZMUH (rottlerin)
RN  - E3B045W6X0 (chelerythrine)
RN  - EC 2.7.1.- (MAP-kinase-activated kinase 2)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - OU13V1EYWQ (SB 203580)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
RN  - SY7Q814VUP (Calcium)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/*analogs & derivatives/pharmacology
MH  - Acetophenones/pharmacology
MH  - Alkaloids
MH  - Androstadienes/pharmacology
MH  - Animals
MH  - Antibodies/pharmacology
MH  - Benzophenanthridines
MH  - Benzopyrans/pharmacology
MH  - Blotting, Western
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Calcium/*metabolism
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Calmodulin/pharmacology
MH  - *Carbazoles
MH  - Cell Nucleus/metabolism
MH  - Chromones/pharmacology
MH  - Cyclic AMP Response Element-Binding Protein/*metabolism
MH  - Cytosol/metabolism
MH  - Enzyme Inhibitors
MH  - Flavonoids/pharmacology
MH  - Hippocampus/cytology/*metabolism
MH  - Imidazoles/pharmacology
MH  - Immunohistochemistry
MH  - In Vitro Techniques
MH  - Indoles/pharmacology
MH  - Intracellular Signaling Peptides and Proteins
MH  - Male
MH  - Morpholines/pharmacology
MH  - Naphthalenes/pharmacology
MH  - Phenanthridines/pharmacology
MH  - Phosphorylation
MH  - Precipitin Tests
MH  - Protein Serine-Threonine Kinases/immunology
MH  - Pyridines/pharmacology
MH  - Pyrroles/pharmacology
MH  - Rats
MH  - Signal Transduction/*physiology
MH  - Time Factors
MH  - Tyrphostins/pharmacology
MH  - Wortmannin
EDAT- 2003/04/18 05:00
MHDA- 2003/06/17 05:00
CRDT- 2003/04/18 05:00
PHST- 2003/04/18 05:00 [pubmed]
PHST- 2003/06/17 05:00 [medline]
PHST- 2003/04/18 05:00 [entrez]
AID - S0306452202009636 [pii]
AID - 10.1016/s0306-4522(02)00963-6 [doi]
PST - ppublish
SO  - Neuroscience. 2003;118(2):477-90. doi: 10.1016/s0306-4522(02)00963-6.