title: Membrane association of estrogen receptor alpha mediates estrogen effect on MAPK activation.
abstract: Estrogen rapidly activates MAPK in many cell types but the mechanisms have not been fully understood. We previously demonstrated that 17-beta-estradiol (estradiol) rapidly induced membrane translocation of estrogen receptor alpha (ERalpha) and activated MAPK in MCF-7 breast cancer cells. This study further determines the cause and effect relationship between the presence of membrane ERalpha and MAPK activation. ERalpha with a membrane localization signal (HE241G-mem) was expressed and compared with the ones in nucleus (HEGO) or cytosol (HE241G) localization. Confocal microscopy showed that HE241G-mem was expressed in the cell membrane as well as in the cytosol in COS-1 cells. HE241G localized in the cytosol and HEGO in the nucleus. Functional studies showed that only membrane ERalpha, not cytosol and nuclear ones, responded to estradiol by inducing MAPK phosphorylation. HE241G-mem neither increased basal nor estradiol-induced ERE promoter activation, indicating no transcriptional action involved. Our data support the view that membrane-associated ERalpha is critical in estrogen-initiated MAPK activation.
authors.affiliation: Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Bernhard
authors.initials: B
authors.lastname: Maier
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Santen
authors.forename: Robert X-D
authors.initials: RX
authors.lastname: Song
mesh_terms: D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D004789:Enzyme Activation; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011960:Receptors, Estrogen / Q000032:analysis / Q000378:metabolism*; D020218:Response Elements
chemical_list: D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen; D004958:Estradiol; D020928:Mitogen-Activated Protein Kinases