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J Biol Chem. 1995 Sep 29;270(39):22783-7.

alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, but not N-methyl-D-aspartate, activates mitogen-activated protein kinase through G-protein beta gamma subunits in rat cortical neurons.

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  • 1Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario.


alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor channels play important roles in plasticity, neurotransmission, and neurotoxicity in the central nervous system. AMPA, but not N-methyl-D-aspartate (NMDA), receptor signaling in rat cortical neurons was found to involve a G-protein coupled to a protein kinase cascade. While both NMDA and AMPA activated p42 mitogen-activated protein kinase (MAPK) in neurons, only AMPA-induced MAPK was inhibited by pertussis toxin. AMPA, but not NMDA, caused an association of a G-protein beta subunit with a Ras, Raf kinase, and MAP/ERK kinase (MEK)-1 complex. The evidence indicates that AMPA triggers MAPK activation via a novel mechanism in which G-protein beta gamma dimers released from G alpha bind to a Ras protein complex causing the activation of Ras, Raf kinase, MEK-1, and finally MAPK.

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