MAP kinase additively activates the mouse Per1 gene promoter with CaM kinase II

Kazumi Nomura, Yusuke Takeuchi, Kohji Fukunaga

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


In a previous study, we showed that the Ca2+/calmodulin-dependent protein kinase IIδ (CaMKIIδ) activates the mouse Per1 (mPer1) promoter through a 5′-GAGGGG-3′ motif near exon1B. Here we use luciferase reporter gene assays to document additive activation of the mPer1 promoter by CaMKIIδ and mitogen-activated protein kinase (MAPK) pathways. Transfection of constitutively active MEKK markedly increased mPer1 promoter activity in NB2A cells. Experiments using MAPK inhibitors and dominant-negative c-Jun NH2-terminal kinase 1 (JNK1) showed that extracellular signal-regulated kinase (ERK) accounts for MEKK-induced mPer1 gene activation. We next defined the ERK-responsive region in the mPer1 promoter. A region from - 1735 to - 1721 was required for ERK-induced promoter activation. We also identified a CaMKII-responsive element near exon 1B. Although mutation of the CaMKII-responsive element has no effect on the ERK responsiveness, elimination of a GC-rich sequence downstream of the CaMKII-responsive region totally abolished ERK responsiveness. Finally, ERK-induced promoter activation was additively potentiated by co-transfection with active CaMKIIδ. These results suggest that additive activation by ERK and CaMKII, most likely as a result of photic stimulation in the suprachiasmatic nucleus, plays a critical role in activating the mPer1 gene promoter.

Original languageEnglish
Pages (from-to)25-33
Number of pages9
JournalBrain research
Issue number1
Publication statusPublished - 2006 Nov 6
Externally publishedYes


  • CaM kinase IIδ
  • Circadian rhythm
  • ERK
  • Period gene
  • Suprachiasmatic nucleus

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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