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PMID: 15955845 Published · ppublish English Journal Article

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

The Journal of cell biology ·Vol. 169 ·No. 6 ·2005-06-20 ·Pages 885-96

Kino T, Tiulpakov A, Ichijo T, Chheng L, Kozasa T, Chrousos GP

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,metabolism Cell Nucleus/genetics,metabolism Chlorocebus aethiops Dexamethasone/pharmacology GTP-Binding Protein beta Subunits/metabolism GTP-Binding Protein gamma Subunits/genetics,metabolism GTP-Binding Proteins Glucocorticoids/metabolism HCT116 Cells HeLa Cells Humans Macromolecular Substances Neoplasm Proteins/genetics,metabolism Promoter Regions, Genetic/genetics Protein Transport/drug effects,physiology Rats Receptors for Activated C Kinase Receptors, Cell Surface/metabolism Receptors, Glucocorticoid/metabolism Repressor Proteins/metabolism Response Elements/drug effects,genetics Somatostatin/pharmacology Transcriptional Activation/genetics
Chemicals
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
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Kino Tomoshige
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
Tiulpakov Anatoly
Ichijo Takamasa
Chheng Ly
Kozasa Tohru
Chrousos George P
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200409150
Email
kinot@mail.nih.gov
Published
2005-06-20
Epub
2005-00-13
Pages
885-96
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2171637
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.200409150 PMC Full Text View journal details
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