Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17126-31. Epub 2004 Nov 29.

Striatin assembles a membrane signaling complex necessary for rapid, nongenomic activation of endothelial NO synthase by estrogen receptor alpha.

Author information

  • 1Molecular Cardiology Research Institute, Department of Medicine, Tufts New England Medical Center, Boston, MA 02111, USA.

Abstract

Steroid hormone receptors (SHRs) are ligand-activated transcription factors that regulate gene expression. SHRs also mediate rapid, nongenomic cellular activation by steroids. In vascular endothelial cells, the SHR for estrogen, estrogen receptor (ER) alpha, is targeted by unknown mechanisms to a functional signaling module in membrane caveolae that enables estrogen to rapidly activate the mitogen-activated protein kinase and phosphatidylinositol 3-Akt kinase pathways, and endothelial NO synthase (eNOS). Here we identify the 110-kDa caveolin-binding protein striatin as the molecular anchor that localizes ERalpha to the membrane and organizes the ERalpha-eNOS membrane signaling complex. Striatin directly binds to amino acids 183-253 of ERalpha, targets ERalpha to the cell membrane, and serves as a scaffold for the formation of an ERalpha-Galphai complex. Disruption of complex formation between ERalpha and striatin blocks estrogen-induced rapid activation mitogen-activated protein kinase, Akt kinase, and eNOS, but has no effect on ER-dependent regulation of an estrogen response element-driven reporter plasmid. These findings identify striatin as a molecular scaffold required for rapid, nongenomic estrogen-mediated activation of downstream signaling pathways. Furthermore, by demonstrating independent regulation of nongenomic vs. genomic ER-dependent signaling, these findings provide conceptual support for the potential development of "pathway-specific" selective ER modulators.

PMID:
15569929
[PubMed - indexed for MEDLINE]
PMCID:
PMC534607
Free PMC Article

Images from this publication.See all images (4)Free text

Fig. 1.
Fig. 4.
Fig. 2.
Fig. 3.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk