Direct interactions with G α i and G βγ mediate nongenomic signaling by estrogen receptor α - PubMed (original) (raw)
. 2007 Jun;21(6):1370-80.
doi: 10.1210/me.2006-0360. Epub 2007 Apr 3.
Affiliations
- PMID: 17405905
- DOI: 10.1210/me.2006-0360
Direct interactions with G α i and G βγ mediate nongenomic signaling by estrogen receptor α
Premlata Kumar et al. Mol Endocrinol. 2007 Jun.
Abstract
Estrogen induces G protein-dependent nongenomic signaling in a variety of cell types via the activation of a plasma membrane-associated subpopulation of estrogen receptor alpha (ER alpha). Using pull-down experiments with purified recombinant proteins, we now demonstrate that ER alpha binds directly to G alpha i and G betagamma. Mutagenesis and the addition of blocking peptide reveals that this occurs via amino acids 251-260 and 271-595 of ER alpha, respectively. Studies of ER alpha complexed with heterotrimeric G proteins further show that estradiol causes the release of both G alpha i and G betagamma without stimulating GTP binding to G alpha i. Moreover, in COS-7 cells, the disruption of ER alpha-G alpha i interaction by deletion mutagenesis of ER alpha or expression of blocking peptide, as well as G betagamma sequestration with beta-adrenergic receptor kinase C terminus, prevents nongenomic responses to estradiol including src and erk activation. In endothelial cells, the disruption of ER alpha-G alpha i interaction prevents estradiol-induced nitric oxide synthase activation and the resulting attenuation of monocyte adhesion that contributes to estrogen-related cardiovascular protection. Thus, through direct interactions, ER alpha mediates a novel mechanism of G protein activation that provides greater diversity of function of both the steroid hormone receptor and G proteins.
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