Involvement of Protein Kinase C in Ca2+‐Signaling Pathways to Activation of AP‐1 DNA‐Binding Activity Evoked via NMDA‐ and Voltage‐Gated Ca2+ Channels

Ken‐ichi ‐i Ohtani, Hiroaki Sakurai, Esther Oh, Emi Iwata, Tomofusa Tsuchiya, Masaaki Tsuda

Research output: Contribution to journalArticlepeer-review


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 Ca2+‐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 Ca2+‐signaling pathways for the increase in TRE‐binding activity coupled with the activation of NMDA‐ and non‐NMDA receptors.

Original languageEnglish (US)
Pages (from-to)605-614
Number of pages10
JournalJournal of Neurochemistry
Issue number2
StatePublished - Aug 1995
Externally publishedYes


  • AP‐1
  • Ca influx
  • Cerebellar granule cells
  • Glutamate receptors
  • Protein kinase C
  • c‐fos induction

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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