Differential regulation of NF-κB, SRE and CRE by dopamine D1 and D2 receptors in transfected NG108-15 cells

Yusuke Takeuchi, Kohji Fukunaga

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

Abstract

To investigate transcriptional regulation by dopamine receptors, we established NG108-15 cells stably expressing D1R, D2LR and D2SR (NGD1R, NGD2LR and NGD2SR) and evaluated the effects of these receptors on NF-κB, SRE and CRE activity using luciferase reporter constructs. Stimulation with quinpirole, a selective D2R agonist, increased NF-κB and SRE activity but decreased CRE activity in both NGD2R cell lines. By contrast, stimulation with SKF 38393, a selective D1R agonist, decreased NF-κB and SRE activity but increased CRE activity in NGD1R cells. Stimulation with forskolin and overexpression of constitutively active PKA suppressed NF-κB activity, likely due to D1R stimulation. D2R stimulation activated ERK, and treatment with U1026, a selective MEK inhibitor, eliminated D2R-induced NF-κB activation. D2R stimulation also activated the neural cell adhesion molecule (NCAM) promoter, which includes a potential NF-κB site. Furthermore, by transfecting constitutively active CaM KII and MEKK, and dominant negative p38 MAPK, we show that the NCAM promoter is positively regulated by CaM KII but negatively regulated by p38 MAPK. These results indicate that D2R-induced NF-κB activation through ERK may be involved in activation of the NCAM promoter, and additionally that other protein kinases such as CaM KII and p38 MAPK also regulate NCAM expression.

Original languageEnglish
Pages (from-to)729-739
Number of pages11
JournalJournal of Neurochemistry
Volume85
Issue number3
DOIs
Publication statusPublished - 2003 May

Keywords

  • Dopamine receptor
  • Mitogen-activated protein kinase
  • NF-κB
  • NG108-15 cells
  • Neuronal cell adhesion molecule

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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