Dopamine D2 receptor activates extracellular signal-regulated kinase through the specific region in the third cytoplasmic loop

Yusuke Takeuchi, Kohji Fukunaga

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

To investigate whether the third cytoplasmic loop and the C-terminal cytoplasmic tail of dopamine D2 receptor (D2R) are involved in extracellular signal-regulated kinase (ERK) activation and subsequent regulation of transcription factors, we established NG108-15 cells stably expressing D2LR and D2SR deleted 40 amino acid residues in the third cytoplasmic loop (NGD2LR-3rd-dele and NGD2SR-3rd-dele) or the C-terminal cytoplasmic tail (NGD2LR-C-dele and NGD2SR-C-dele) and evaluated these receptors' functions using luciferase reporter gene assay. Immunocytochemical studies showed similar intracellular distributions of D2LR-3rd-dele and D2SR-3rd-dele to D2LR and D2SR, respectively. Quinpirole-induced inhibition of forskolin-induced cyclic AMP responsive element (CRE) activation was not affected by the deletion of 40 amino acid residues. However, nuclear factor-kappa B (NF-κB) activation by D2R-3rd-dele was largely attenuated compared to that by D2R. Similarly, ERK or serum-responsive element (SRE) activation by quinpirole treatment was totally abolished in NGD2R-3rd-dele cells. Moreover, D2R-C-dele was diffusely distributed or clustered in the cell bodies and lost the receptor functions. Taken together, the 40 amino acid residues in the third cytoplasmic loop are essential for the ERK activation but not for inhibition of adenylyl cyclase through Gi/o proteins. In addition, the C-terminal cytoplasmic tail is essential for membrane association of D2Rs to elicit the receptor functions.

Original languageEnglish
Pages (from-to)1498-1507
Number of pages10
JournalJournal of Neurochemistry
Volume89
Issue number6
DOIs
Publication statusPublished - 2004 Jun

Keywords

  • C-terminal cytoplasmic tail
  • Dopamine receptor
  • ERK
  • NG108-15 cells
  • Third cytoplasmic loop

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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