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Published online 13 June 2005. doi:10.1083/jcb.200409150
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 169, Number 6, 885-896
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Article

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

Tomoshige Kino1, Anatoly Tiulpakov1, Takamasa Ichijo1, Ly Chheng1, Tohru Kozasa2, and George P. Chrousos1

1 Reproductive Biology and Medicine Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892
2 Department of Pharmacology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612

Correspondence to Tomoshige Kino: kinot{at}mail.nih.gov

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 receptor-activated WD-repeat Gß interacts with the glucocorticoid receptor (GR), comigrates with it into the nucleus and suppresses GR-induced transactivation of the glucocorticoid-responsive genes. Association of G{gamma} with Gß is necessary for this action of Gß. Both endogenous and enhanced green fluorescent protein (EGFP)–fused Gß2 and G{gamma}2 proteins were detected in the nucleus at baseline, whereas a fraction of EGFP-Gß2 and DsRed2-GR comigrated to the nucleus or the plasma membrane, depending on the exposure of cells to dexamethasone or somatostatin, respectively. Gß2 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 Gß{gamma} complex interacts with the GR and suppresses its transcriptional activity by associating with the transcriptional complex formed on GR-responsive promoters.

Abbreviations used in this paper: AF, activation function; ChIP, chromatin immunoprecipitation; DBD, DNA-binding domain; G protein: guanine nucleotide-binding protein; GPCR, G protein–coupled receptor; GR, glucocorticoid receptor; GRE, glucocorticoid response element; MMTV, mouse mammary tumor virus; NES, nuclear export signal; RACK1, receptor for activated C-kinase 1; RPLP0, ribosomal phosphoprotein P0; siRNA, short interfering RNA; SSTR2, somatostatin receptor type 2; TAT, tyrosine aminotransferase.


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