G protein beta 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

doi:10.1083/jcb.200409150

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

J Cell Biol. 2005 Jun 20;169(6):885-96. doi: 10.1083/jcb.200409150. Epub 2005 Jun 13.

Authors

Tomoshige Kino¹, Anatoly Tiulpakov, Takamasa Ichijo, Ly Chheng, Tohru Kozasa, George P Chrousos

Affiliation

¹ Reproductive Biology and Medicine Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. kinot@mail.nih.gov

Abstract

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 Gbeta interacts with the glucocorticoid receptor (GR), comigrates with it into the nucleus and suppresses GR-induced transactivation of the glucocorticoid-responsive genes. Association of Ggamma with Gbeta is necessary for this action of Gbeta. Both endogenous and enhanced green fluorescent protein (EGFP)-fused Gbeta2 and Ggamma2 proteins were detected in the nucleus at baseline, whereas a fraction of EGFP-Gbeta2 and DsRed2-GR comigrated to the nucleus or the plasma membrane, depending on the exposure of cells to dexamethasone or somatostatin, respectively. Gbeta2 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 Gbetagamma complex interacts with the GR and suppresses its transcriptional activity by associating with the transcriptional complex formed on GR-responsive promoters.

MeSH terms

Active Transport, Cell Nucleus / genetics
Animals
COS Cells
Cell Membrane / genetics
Cell Membrane / metabolism
Cell Nucleus / genetics
Cell Nucleus / metabolism*
Chlorocebus aethiops
Dexamethasone / pharmacology
GTP-Binding Protein beta Subunits / metabolism*
GTP-Binding Protein gamma Subunits / genetics
GTP-Binding Protein gamma Subunits / metabolism
GTP-Binding Proteins
Glucocorticoids / metabolism
HCT116 Cells
HeLa Cells
Humans
Macromolecular Substances
Neoplasm Proteins / genetics
Neoplasm Proteins / metabolism
Promoter Regions, Genetic / genetics
Protein Transport / drug effects
Protein Transport / physiology
Rats
Receptors for Activated C Kinase
Receptors, Cell Surface / metabolism*
Receptors, Glucocorticoid / metabolism*
Repressor Proteins / metabolism*
Response Elements / drug effects
Response Elements / genetics
Somatostatin / pharmacology
Transcriptional Activation / genetics*

Substances

GTP-Binding Protein beta Subunits
GTP-Binding Protein gamma Subunits
Glucocorticoids
Macromolecular Substances
Neoplasm Proteins
RACK1 protein, human
Receptors for Activated C Kinase
Receptors, Cell Surface
Receptors, Glucocorticoid
Repressor Proteins
Somatostatin
Dexamethasone
GTP-Binding Proteins