Glutamate-dependent transcriptional regulation of the chkbp gene:: Signaling mechanisms

Glutamate, the major excitatory neurotransmitter, induces a signal from the membrane to the nucleus that regulates gene expression. The gene encoding the chick kainate binding protein undergoes a glutamate-dependent transcriptional regulation via an activator protein-1 site within its promoter region. To characterize this event, cultured chick Bergmann glia cells were exposed to glutamate, and a dose-dependent increase in promoter activity was established. The glutamate effect is mediated through Ca2+-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptors. The signaling 2 cascade includes phosphatidyl inositol 3-kinase, Ca2+/calmodulin-dependent protein kinase II, mitogen-activated protein kinase, and p90 ribosomal S6 kinase activation. The cAMP response-element binding protein becomes phosphorylated and activates fos transcription. Finally, the activator protein-1 complex binds to the glutamate response element in the chick kainate binding protein promoter region inducing its activity. We propose that the mitogen-activated protein kinase/p90 ribosomal S6 kinase pathway plays a critical role in glutamate-induced gene transcription. (C) 2002 Wiley-Liss, Inc.