G protein β interacts with the glucocorticoid receptor and suppresses its transcriptional activity in the nucleus

Tomoshige Kino, Anatoly Tiulpakov, Takamasa Ichijo, Ly Chheng, Tohru Kozasa, George P. Chrousos

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88 Citations (Scopus)


Extracellular stimuli that activate cell surface receptors modulate glucocorticoid actions via as yet unclear mechanisms. Here, we report that the guanine nucleotide-binding protein (G protein)-coupled receptoractivated WD-repeat Gβ interacts with the glucocorticoid receptor (GR), comigrates with it into the nucleus and suppresses GR-induced transactivation of the glucocorticoid-responsive genes. Association of Gγ with Gβ is necessary for this action of Gβ. Both endogenous and enhanced green fluorescent protein (EGFP)-fused Gβ2 and Gγ2 proteins were detected in the nucleus at baseline, whereas a fraction of EGFP-Gβ2 and DsRed2-GR comigrated to the nucleus or the plasma membrane, depending on the exposure of cells to dexamethasone or somatostatin, respectively. Gβ2 was associated with GR/glucocorticoid response elements (GREs) in vivo and suppressed activation function-2-directed transcriptional activity of the GR. We conclude that the Gβγ complex interacts with the GR and suppresses its transcriptional activity by associating with the transcriptional complex formed on GR-responsive promoters.

Original languageEnglish
Pages (from-to)885-896
Number of pages12
JournalJournal of Cell Biology
Issue number6
Publication statusPublished - 1 Jun 2005


ASJC Scopus subject areas

  • Cell Biology

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