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A novel function of Goα: mediation of extracellular signal‐regulated kinase activation by opioid receptors in neural cells
Author(s) -
Zhang WenBo,
Zhang Zhe,
Ni YanXiang,
Wu YaLan,
Pei Gang
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.01930.x
Subject(s) - microbiology and biotechnology , extracellular , signal transduction , biology , kinase , receptor , biochemistry
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 Goα 1 , but not Giα 2 , 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 Giα 2 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 Goα 1 and Goα 2 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.