Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase

Tommaso Simoncini, Ali Hafezi-Moghadam, Derek P. Brazil, Klaus Ley, William W. Chin and James K. Liao ()
Additional contact information
Tommaso Simoncini: Cardiovascular and
Ali Hafezi-Moghadam: Department of Biomedical Engineering University of Virginia Health Sciences Center
Derek P. Brazil: Howard Hughes Medical Institute, Joslin Diabetes Center
Klaus Ley: Department of Biomedical Engineering University of Virginia Health Sciences Center
William W. Chin: Brigham & Women's Hospital and Harvard Medical School
James K. Liao: Cardiovascular and

Nature, 2000, vol. 407, issue 6803, 538-541

Abstract: Abstract Oestrogen produces diverse biological effects through binding to the oestrogen receptor (ER)1. The ER is a steroid hormone nuclear receptor, which, when bound to oestrogen, modulates the transcriptional activity of target genes2. Controversy exists, however, concerning whether ER has a role outside the nucleus3, particularly in mediating the cardiovascular protective effects of oestrogen4. Here we show that the ER isoform, ERα, binds in a ligand-dependent manner to the p85α regulatory subunit of phosphatidylinositol-3-OH kinase (PI(3)K). Stimulation with oestrogen increases ERα-associated PI(3)K activity, leading to the activation of protein kinase B/Akt and endothelial nitric oxide synthase (eNOS). Recruitment and activation of PI(3)K by ligand-bound ERα are independent of gene transcription, do not involve phosphotyrosine adapter molecules or src-homology domains of p85α, and extend to other steroid hormone receptors. Mice treated with oestrogen show increased eNOS activity and decreased vascular leukocyte accumulation after ischaemia and reperfusion injury. This vascular protective effect of oestrogen was abolished in the presence of PI(3)K or eNOS inhibitors. Our findings define a physiologically important non-nuclear oestrogen-signalling pathway involving the direct interaction of ERα with PI(3)K.

Date: 2000
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/35035131 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:407:y:2000:i:6803:d:10.1038_35035131

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/35035131

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().