A novel function of Goα: Mediation of extracellular signal-regulated kinase activation by opioid receptors in neural cells

Wen Bo Zhang, Zhe Zhang, Yan Xiang Ni, Ya Lan Wu, Gang Pei

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Go is the most abundant G protein expressed in brain but its function is less known. Here we show a novel function of Goα as a mediator of opioid receptor-induced extracellular signal-regulated kinase activation in neural cells. The current study found that, in neuroblastoma × glioma NG108-15 hybrid cells, activation of extracellular signal-regulated kinase through delta opioid receptors was mediated by pertussis toxin-sensitive G protein and independent of Gβγ subunits, PI3 kinase and receptor internalization. Overexpression of a dominant negative form of Goα1, but not Giα2, completely blocked delta opioid receptor-induced extracellular signal-regulated kinase activity. Decreasing Goα expression by RNA interference greatly reduced delta opioid receptor-induced extracellular signal-regulated kinase activity and extracellular signal-regulated kinase-dependent gene expression, while knocking down Giα2 did not. By taking advantage of differences between human and mouse Goα gene sequences, we simultaneously knocked down endogenous Goα expression and expressed exogenous human Goα subunits. We found that both human Goα1 and Goα2 could mediate delta opioid receptor-induced extracellular signal-regulated kinase activation. This study suggests that one of the functions of Goα in the brain is to mediate extracellular signal-regulated kinase activation by G protein-coupled receptors.

Original languageEnglish (US)
Pages (from-to)1213-1222
Number of pages10
JournalJournal of neurochemistry
Volume86
Issue number5
DOIs
StatePublished - Sep 2003
Externally publishedYes

Keywords

  • Delta opioid receptors
  • Dominant negative
  • Extracellular signal-regulated kinase
  • Goα
  • RNA interference

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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