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Developmentally regulated role for Ras‐GRFs in coupling NMDA glutamate receptors to Ras, Erk and CREB
Author(s) -
Tian Xuejun,
Gotoh Takaya,
Tsuji Kiyoshi,
Lo Eng H,
Huang Su,
Feig Larry A
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600151
Subject(s) - creb , guanine nucleotide exchange factor , biology , mapk/erk pathway , nmda receptor , neuroprotection , glutamate receptor , microbiology and biotechnology , neuroscience , transcription factor , receptor , gtpase , signal transduction , biochemistry , gene
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.