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PMID: 11517234 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Requirement of Ras for the activation of mitogen-activated protein kinase by calcium influx, cAMP, and neurotrophin in hippocampal neurons.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 21 ·No. 17 ·2001-09-01 ·Pages 6459-66

Iida N, Namikawa K, Kiyama H, Ueno H, Nakamura S, Hattori S

Abstract

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.

MeSH Terms
Adenoviridae/genetics Animals Brain-Derived Neurotrophic Factor/pharmacology Calcium/metabolism Cells, Cultured Colforsin/pharmacology Cyclic AMP/metabolism Cyclic AMP Response Element-Binding Protein/metabolism Dose-Response Relationship, Drug Enzyme Activation/drug effects Enzyme Inhibitors/pharmacology Genes, Dominant Hippocampus/cytology,drug effects,metabolism Ionophores/pharmacology Mitogen-Activated Protein Kinases/metabolism N-Methylaspartate/pharmacology Nerve Growth Factors/metabolism Neurons/cytology,drug effects,metabolism Phosphorylation/drug effects Rats Signal Transduction/drug effects Transfection rap1 GTP-Binding Proteins ras GTPase-Activating Proteins/biosynthesis,genetics ras Proteins/genetics,metabolism
Chemicals
Brain-Derived Neurotrophic Factor Cyclic AMP Response Element-Binding Protein Enzyme Inhibitors Ionophores Nerve Growth Factors ras GTPase-Activating Proteins Colforsin N-Methylaspartate Cyclic AMP Mitogen-Activated Protein Kinases rap1 GTP-Binding Proteins ras Proteins Calcium
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Iida N
Division of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan.
Namikawa K
Kiyama H
Ueno H
Nakamura S
Hattori S
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2001-09-01
Pages
6459-66
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6763070
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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