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 Ca(2+)-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptors. The signaling cascade includes phosphatidyl inositol 3-kinase, Ca(2+)/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.
Aguirre
Adán
A
Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México DF, México.
López-Bayghen
Esther
E
Ortega
Arturo
A
D000818:Animals; D015153:Blotting, Western; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002478:Cells, Cultured; D002642:Chick Embryo; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D018698:Glutamic Acid / Q000494:pharmacology*; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic / Q000235:genetics; D011493:Protein Kinase C / Q000502:physiology; D018091:Receptors, AMPA / Q000502:physiology; D018092:Kainic Acid Receptors / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D017871:Calcium-Calmodulin-Dependent Protein Kinases; D015500:Chloramphenicol O-Acetyltransferase; D017362:Cyclic AMP Response Element-Binding Protein; D018698:Glutamic Acid; D011493:Protein Kinase C; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D011993:Recombinant Fusion Proteins; D019893:Ribosomal Protein S6 Kinases