PMID- 11517234
OWN - NLM
STAT- MEDLINE
DCOM- 20010920
LR  - 20191023
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 21
IP  - 17
DP  - 2001 Sep 1
TI  - Requirement of Ras for the activation of mitogen-activated protein kinase by 
      calcium influx, cAMP, and neurotrophin in hippocampal neurons.
PG  - 6459-66
AB  - Mitogen-activated protein (MAP) kinase plays important roles in the establishment 
      of long-term potentiation both in vitro and in living animals. MAP kinase is 
      activated in response to a broad range of stimuli, including calcium influx 
      through NMDA receptor and L-type calcium channel, cAMP, and neurotrophins. To 
      investigate the role of Ras in the activation of MAP kinase and cAMP response 
      element-binding protein (CREB) in hippocampal neurons, we inhibited Ras function 
      by overexpressing a Ras GTPase-activating protein, Gap1(m), or dominant negative 
      Ras by means of adenovirus vectors. Gap1(m) expression almost completely 
      suppressed MAP kinase activation in response to NMDA, calcium ionophore, membrane 
      depolarization, forskolin, and brain-derived neurotrophic factor (BDNF). Dominant 
      negative Ras also showed similar effects. On the other hand, Rap1GAP did not 
      significantly inhibit the forskolin-induced activation of MAP kinase. In contrast 
      to MAP kinase activation, the inactivation of Ras activity did not inhibit 
      significantly NMDA-induced CREB phosphorylation, whereas BDNF-induced CREB 
      phosphorylation was inhibited almost completely. These results demonstrate that 
      Ras transduces signals elicited by a broad range of stimuli to MAP kinase in 
      hippocampal neurons and further suggest that CREB phosphorylation depends on 
      multiple pathways.
FAU - Iida, N
AU  - Iida N
AD  - Division of Biochemistry and Cellular Biology, National Institute of 
      Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 
      187-8502, Japan.
FAU - Namikawa, K
AU  - Namikawa K
FAU - Kiyama, H
AU  - Kiyama H
FAU - Ueno, H
AU  - Ueno H
FAU - Nakamura, S
AU  - Nakamura S
FAU - Hattori, S
AU  - Hattori S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Ionophores)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (ras GTPase-Activating Proteins)
RN  - 1F7A44V6OU (Colforsin)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.6.5.2 (rap1 GTP-Binding Proteins)
RN  - EC 3.6.5.2 (ras Proteins)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/pharmacology
MH  - Calcium/metabolism
MH  - Cells, Cultured
MH  - Colforsin/pharmacology
MH  - Cyclic AMP/metabolism
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Activation/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Genes, Dominant
MH  - Hippocampus/cytology/drug effects/*metabolism
MH  - Ionophores/pharmacology
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - N-Methylaspartate/pharmacology
MH  - Nerve Growth Factors/*metabolism
MH  - Neurons/cytology/drug effects/*metabolism
MH  - Phosphorylation/drug effects
MH  - Rats
MH  - Signal Transduction/drug effects
MH  - Transfection
MH  - rap1 GTP-Binding Proteins
MH  - ras GTPase-Activating Proteins/biosynthesis/genetics
MH  - ras Proteins/genetics/*metabolism
PMC - PMC6763070
EDAT- 2001/08/23 10:00
MHDA- 2001/09/21 10:01
PMCR- 2002/03/01
CRDT- 2001/08/23 10:00
PHST- 2001/08/23 10:00 [pubmed]
PHST- 2001/09/21 10:01 [medline]
PHST- 2001/08/23 10:00 [entrez]
PHST- 2002/03/01 00:00 [pmc-release]
AID - 21/17/6459 [pii]
AID - 5557 [pii]
AID - 10.1523/JNEUROSCI.21-17-06459.2001 [doi]
PST - ppublish
SO  - J Neurosci. 2001 Sep 1;21(17):6459-66. doi: 10.1523/JNEUROSCI.21-17-06459.2001.