HUMAN METABOTROPIC GLUTAMATE-RECEPTOR-2 COUPLES TO THE MAP KINASE CASCADE IN CHINESE-HAMSTER OVARY CELLS

WE have examined the functional coupling of the human metabotropic glu tamate receptor type 2 (mGluR2) with the regulation of the mitogen act ivated protein kinase (MAP kinase) signal transduction cascade. We dem onstrated that L-glutamate stimulation of the human mGluR2 receptor tr ansiently expressed in chinese hamster ovary (CHO) cells leads to a ra pid increase in the activity of p42/p44 MAP kinase (also known as the extracellular signal regulated kinases, ERK1 and ERK2). Activation of p42/p44 MAP kinase has been demonstrated in a peptide phosphorylation assay and through the demonstration of a shift in electrophoretic mobi lity of p42 MAP kinase following activation. In both assay systems L-g lutamate stimulation of MAP kinase was inhibited by pertussis toxin an d by the MEK (MAP/ERK activating kinase) inhibitor PD 98059. We conclu de that L-glutamate stimulation of the mGluR2 receptor in CHO cells me diated regulation of p42/p44 MAP kinase following the activation of pe rtussis toxin-sensitive G alpha(i) G-proteins via a distinct protein k inase signalling pathway that utilizes MEK. NeuroReport 9: 2335-2339 ( C) 1998 Rapid Science Ltd.