ArticleProceedings of the National Academy of Sciences of the United States of America2003
Plasma membrane localization and function of the estrogen receptor alpha variant (ER46) in human endothelial cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 173 papers.
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Who cites it
173 citing papers in PubMed, 451 citations in OpenAlex.
- Targeting estrogen receptor alpha in breast cancer for novel therapies resistance mechanisms and future directions.Discover oncology · 2025Review
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- Hormone Replacement Therapy and Cardiovascular Health in Postmenopausal Women.International journal of molecular sciences · 2025Review
- Protein lipidation in the tumor microenvironment: enzymology, signaling pathways, and therapeutics.Molecular cancer · 2025Review
- Decoding estrogen receptor and GPER biology: structural insights and therapeutic advances in ERα-positive breast cancer.Frontiers in oncology · 2025Review
- Estrogen Receptor Alpha Mutations, Truncations, Heterodimers, and Therapies.Endocrinology · 2024Review
- URAT1 is expressed in cardiomyocytes and dotinurad attenuates the development of diet-induced metabolic heart disease.iScience · 2023Article
- Review
- A Basic Review on Estrogen Receptor Signaling Pathways in Breast Cancer.International journal of molecular sciences · 2023Review
- Knockout of murine Lyplal1 confers sex-specific protection against diet-induced obesity.Journal of molecular endocrinology · 2023Article
- Sex differences in cardiovascular response to sepsis.American journal of physiology. Cell physiology · 2023Review
- The emerging role of estrogen's non-nuclear signaling in the cardiovascular disease.Frontiers in cardiovascular medicine · 2023Review
- ESR1 activating mutations: From structure to clinical application.Biochimica et biophysica acta. Reviews on cancer · 2023Review
- Macrophages Upregulate Estrogen Receptor Expression in the Model of Obesity-Associated Breast Carcinoma.Cells · 2022Article
- Catalase, a therapeutic target in the reversal of estrogen-mediated aging.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Sexual dimorphism in cardiac remodeling: the molecular mechanisms ruled by sex hormones in the heart.Journal of molecular medicine (Berlin, Germany) · 2022Review
- Estrogen Receptors-Mediated Apoptosis in Hormone-Dependent Cancers.International journal of molecular sciences · 2022Review
- Estrogen Receptors as Molecular Targets of Endocrine Therapy for Glioblastoma.International journal of molecular sciences · 2021Review
- Estrogen receptor variant ERα46 and insulin receptor drive in primary breast cancer cells growth effects and interleukin 11 induction prompting the motility of cancer-associated fibroblasts.Clinical and translational medicine · 2021Article
- HPTE-Induced Embryonic Thymocyte Death and Alteration of Differentiation Is Not Rescued by ERα or GPER Inhibition but Is Exacerbated by Concurrent TCR Signaling.International journal of molecular sciences · 2021Article
113 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Estrogen receptor (ER) alpha variants have been identified in an array of nonendothelial cells. We previously demonstrated that estrogen rapidly induces nitric oxide release via a phosphatidylinositol 3-kinase/Akt/endothelial nitric-oxide synthase (eNOS) pathway in EA.hy926 cells (immortalized human endothelial cells), which express a 46-kDa ER. We now confirm that, due to alternative splicing, the 46-kDa endothelial cell protein (ER46) is an amino-terminal truncated product of full-length ER alpha (ER66). ER46 is expressed in the plasma membrane, cytosol, and nucleus of resting, estrogen-deprived cells. Flow cytometric and immunofluorescence microscopic analyses demonstrated that the ER46 C but not N terminus is Ab-accessible in the plasma membrane. Inhibition of palmitoylation with tunicamycin and [(3)H]palmitic acid labeling demonstrated an estrogen-induced, palmitoylation-dependent plasma membrane ER46 recruitment, with reorganization into caveolae. In reconstituted, estrogen-stimulated COS-7 (ER-null) cells, membrane ER46 more efficiently triggered membrane eNOS phosphorylation than ER66. Conversely, ER66 more efficiently mediated estrogen response element reporter-gene transactivation than ER46. These results demonstrate that ER46 is localized and further dynamically targeted to the plasma membrane in a palmitoylation-dependent manner. ER46 more efficiently modulates membrane-initiated estrogen actions, including eNOS activation, than full-length ER66. These findings may have important implications in vascular-specific targeting of estrogen receptor agonists.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.