Developmentally regulated role for Ras-GRFs in coupling NMDA glutamate receptors to Ras, Erk and CREB
- Resource Type
- Authors
- Kiyoshi Tsuji; Eng H. Lo; Takaya Gotoh; Su Huang; Xuejun Tian; Larry A. Feig
- Source
- Subject
- Protein Serine-Threonine Kinases
CREB
Neuroprotection
Receptors, N-Methyl-D-Aspartate
General Biochemistry, Genetics and Molecular Biology
Article
Mice
Ras-GRF1
Animals
Cyclic AMP Response Element-Binding Protein
Extracellular Signal-Regulated MAP Kinases
Molecular Biology
Cells, Cultured
Calcium signaling
Mice, Knockout
Neurons
General Immunology and Microbiology
biology
Arabidopsis Proteins
ras-GRF1
General Neuroscience
Glutamate receptor
Molecular biology
Cell biology
Enzyme Activation
Stroke
nervous system
Animals, Newborn
Knockout mouse
biology.protein
ras Proteins
NMDA receptor
ras Guanine Nucleotide Exchange Factors
Signal transduction
SOS1 Protein
Signal Transduction
- Language
- English
p140 Ras‐GRF1 and p130 Ras‐GRF2 constitute a family of calcium/calmodulin‐regulated guanine–nucleotide exchange factors that activate the Ras GTPases. Studies on mice lacking these exchange factors revealed that both p140 Ras‐GRF1 and p130 Ras‐GRF2 couple NMDA glutamate receptors (NMDARs) to the activation of the Ras/Erk signaling cascade and to the maintenance of CREB transcription factor activity in cortical neurons of adult mice. Consistent with this function for Ras‐GRFs and the known neuroprotective effect of CREB activity, ischemia‐induced CREB activation is reduced in the brains of adult Ras‐GRF knockout mice and neuronal damage is enhanced. Interestingly, in cortical neurons of neonatal animals NMDARs signal through Sos rather than Ras‐GRF exchange factors, implying that Ras‐GRFs endow NMDARs with functions unique to mature neurons.