title: Involvement of protein kinase C in Ca(2+)-signaling pathways to activation of AP-1 DNA-binding activity evoked via NMDA- and voltage-gated Ca2+ channels.
abstract: Stimulation of cultured cerebellar granule cells with N-methyl-D-aspartate (NMDA) or kainic acid (KA) leads to activation of activator protein-1 (AP-1) DNA-binding activity, which can be monitored by an increase in 12-O-tetradecanoylphorbol 13-acetate (TPA)-responsive element (TRE)-binding activity, in concert with c-fos induction. For this increase in TRE-binding activity, Ca2+ influx across the plasma membrane is essential. Treatment of cells with an intracellular Ca2+ chelator, BAPTA-AM, abolished this increase. Close correspondence between the dose-response curves of 45Ca2+ uptake and TRE-binding activity by NMDA or KA suggested that Ca2+ influx not only triggered sequential activation of Ca(2+)-signaling processes leading to the increase in TRE-binding activity, but also controlled its increased level. Stimulation of non-NMDA receptors by KA mainly caused Ca2+ influx through voltage-gated Ca2+ channels, whereas stimulation of NMDA receptors caused Ca2+ influx through NMDA-gated ion channels. The protein kinase C (PKC) inhibitors staurosporine and calphostin C inhibited the increase in TRE-binding activity caused by NMDA and KA at the same concentration at which they inhibited that caused by TPA. Furthermore, down-regulation of PKC inhibited the increase in TRE-binding activity by NMDA and KA. Thus, a common pathway that includes PKC could, at least in part, be involved in the Ca(2+)-signaling pathways for the increase in TRE-binding activity coupled with the activation of NMDA- and non-NMDA receptors.
authors.affiliation: Department of Microbiology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ohtani
authors.forename: H
authors.initials: H
authors.lastname: Sakurai
authors.forename: E
authors.initials: E
authors.lastname: Oh
authors.forename: E
authors.initials: E
authors.lastname: Iwata
authors.forename: T
authors.initials: T
authors.lastname: Tsuchiya
authors.forename: M
authors.initials: M
authors.lastname: Tsuda
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D004247:DNA / Q000378:metabolism*; D004594:Electrophysiology; D015640:Ion Channel Gating; D051379:Mice; D008813:Mice, Inbred ICR; D016202:N-Methylaspartate / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D016202:N-Methylaspartate; D004247:DNA; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium