ArticleMolecular and cellular biology1999
Phosphorylation of human estrogen receptor alpha by protein kinase A regulates dimerization.
Article in Molecular and cellular biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 254 citations in OpenAlex.
- Nucleic sexual hormone receptor signaling pathways in breast cancer: function regulation, crosstalk, and therapeutic implications.NPJ precision oncology · 2026Review
- ChIP happens: from biochemical origins to the modern omics toolbox for understanding steroid hormone receptors.The Biochemical journal · 2026Review
- A bifunctional optical reporter for tracking estrogen response dynamics in neurons.bioRxiv : the preprint server for biology · 2025Article
- Roles of Post-Translational Modifications of Transcription Factors Involved in Breast Cancer Hypoxia.Molecules (Basel, Switzerland) · 2025Review
- Decoding estrogen receptor and GPER biology: structural insights and therapeutic advances in ERα-positive breast cancer.Frontiers in oncology · 2025Review
- Tackling exosome and nuclear receptor interaction: an emerging paradigm in the treatment of chronic diseases.Military Medical Research · 2024Review
- Estrogen Receptor Signaling in Breast Cancer.Cancers · 2023Review
- A Basic Review on Estrogen Receptor Signaling Pathways in Breast Cancer.International journal of molecular sciences · 2023Review
- Neuregulin modulates hormone receptor levels in breast cancer through concerted action on multiple signaling pathways.Clinical science (London, England : 1979) · 2023Article
- Multimerization of the GATA4 transcription factor regulates transcriptional activity and cardiomyocyte hypertrophic response.International journal of biological sciences · 2022Article
- Forskolin Stimulates Estrogen Receptor (ER)International journal of endocrinology · 2022Article
- Upregulation of CYP1B1 by hypoxia is mediated by ERα activation in breast cancer cells.American journal of cancer research · 2022Article
- Article
- Phosphorylation of NANOG by casein kinase I regulates embryonic stem cell self-renewal.FEBS letters · 2021Article
- Checkpoint suppressor 1 suppresses transcriptional activity of ERα and breast cancer cell proliferation via deacetylase SIRT1.Cell death & disease · 2018Article
- Distinct Contributions of Tryptophan Residues within the Dimerization Domain to Nanog Function.Journal of molecular biology · 2017Article
- Epigenetic activation of the prostaglandin receptor EP4 promotes resistance to endocrine therapy for breast cancer.Oncogene · 2017Article
- The Steroid Hormone 20-Hydroxyecdysone Enhances Gene Transcription through the cAMP Response Element-binding Protein (CREB) Signaling Pathway.The Journal of biological chemistry · 2016Article
- G9a-mediated methylation of ERα links the PHF20/MOF histone acetyltransferase complex to hormonal gene expression.Nature communications · 2016Article
- Long-term consequences of estrogens administered in midlife on female cognitive aging.Hormones and behavior · 2015Review
21 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phosphorylation provides an important mechanism by which transcription factor activity is regulated. Estrogen receptor alpha (ERalpha) is phosphorylated on multiple sites, and stimulation of a number of growth factor receptors and/or protein kinases leads to ligand-independent and/or synergistic increase in transcriptional activation by ERalpha in the presence of estrogen. Here we show that ERalpha is phosphorylated by protein kinase A (PKA) on serine-236 within the DNA binding domain. Mutation of serine-236 to glutamic acid prevents DNA binding by inhibiting dimerization by ERalpha, whereas mutation to alanine has little effect on DNA binding or dimerization. Furthermore, PKA overexpression or activation of endogenous PKA inhibits dimerization in the absence of ligand. This inhibition is overcome by the addition of 17beta-estradiol or the partial agonist 4-hydroxy tamoxifen. Interestingly, treatment with the complete antagonist ICI 182,780 does not overcome the inhibitory effect of PKA activation. Our results indicate that in the absence of ligand ERalpha forms dimers through interaction between DNA binding domains and that dimerization mediated by the ligand binding domain only occurs upon ligand binding but that the complete antagonist ICI 182,780 prevents dimerization through the ligand-binding domain. Heterodimer formation between ERalpha and ERbeta is similarly affected by PKA phosphorylation of serine 236 of ERalpha. However, 4-hydroxytamoxifen is unable to overcome inhibition of dimerization by PKA. Thus, phosphorylation of ERalpha in the DNA binding domain provides a mechanism by which dimerization and thereby DNA binding by the estrogen receptor is regulated.
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