Membrane association of estrogen receptor a mediates estrogen effect on MAPK activation

Zhenguo Zhang, Bernhard Maier, Richard J. Santen, Robert X.D. Song

Research output: Contribution to journalArticle

78 Scopus citations


Estrogen rapidly activates MAPK in many cell types but the mechanisms have not been fully understood. We previously demonstrated that 17-β-estradiol (estradiol) rapidly induced membrane translocation of estrogen receptor α (ERα) and activated MAPK in MCF-7 breast cancer cells. This study further determines the cause and effect relationship between the presence of membrane ERα and MAPK activation. ERα 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 ERα, 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 ERα is critical in estrogen-initiated MAPK activation.

Original languageEnglish (US)
Pages (from-to)926-933
Number of pages8
JournalBiochemical and Biophysical Research Communications
Issue number5
StatePublished - Jan 1 2002
Externally publishedYes


  • Estrogen
  • Estrogen receptor
  • MAPK and signal transduction
  • Membrane

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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