Requirements for estrogen receptor α membrane localization and function

The estrogen receptor α (ERα) exists as a functional receptor at the plasma membrane. The structural requirements for localization and function are not well understood. Several laboratories have recently elucidated certain requirements. We recently found the translocation of ERα to the membrane in t...

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Veröffentlicht in:Steroids 2005-05, Vol.70 (5), p.361-363
Hauptverfasser: Evinger, Albert J., Levin, Ellis R.
Format: Artikel
Sprache:eng
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Zusammenfassung:The estrogen receptor α (ERα) exists as a functional receptor at the plasma membrane. The structural requirements for localization and function are not well understood. Several laboratories have recently elucidated certain requirements. We recently found the translocation of ERα to the membrane in the absence of estrogen is dependent on caveolin-1 and serine 522 of the ERα protein. Mutation of serine 522 to alanine results in a 62% decrease in membrane localization and association with caveolin-1. Similarly, deletion of the caveolin-1 scaffolding domain (amino acids 60–100) largely prevents the localization of ERα at the plasma membrane. In the presence of estradiol (E 2), ERα, Src-homology and collagen homology (Shc), and insulin-like growth factor receptor-1 proteins associate with and increase the localization of ERα at the membrane. Membrane-localized ERα functions as an atypical G-protein coupled receptor. There is no good evidence that ERα spans the membrane or contains an extracellular domain. E 2/ERα activates different G-proteins in cell context-related fashion. These G-proteins lead to the activation of Src through PLC, PKC, IP3 and calcium influx. In breast cancer, Src activates matrix metalloproteinase-2 and -9, which cleaves heparin binding epidermal growth factor, and thus activates EGFR. This leads to downstream signaling through ERK and PI3 kinase, imparting cell growth and survival.
ISSN:0039-128X
1878-5867
DOI:10.1016/j.steroids.2005.02.015