Activation of the Estrogen Receptor Through Phosphorylation by Mitogen-Activated Protein Kinase

1995/12/01 by Shigeaki Kato, Hideki Endoh, Yoshikazu Masuhiro +9 · 21 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Estrogen and related hormone effects #Cytokine Signaling Pathways and Interactions #Protein Kinase Regulation and GTPase Signaling

paper · doi:10.1126/science.270.5241.1491

openalex publication_date 1995/12/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28

Abstract

The phosphorylation of the human estrogen receptor (ER) serine residue at position 118 is required for full activity of the ER activation function 1 (AF-1). This Ser118 is phosphorylated by mitogen-activated protein kinase (MAPK) in vitro and in cells treated with epidermal growth factor (EGF) and insulin-like growth factor (IGF) in vivo. Overexpression of MAPK kinase (MAPKK) or of the guanine nucleotide binding protein Ras, both of which activate MAPK, enhanced estrogen-induced and antiestrogen (tamoxifen)-induced transcriptional activity of wild-type ER, but not that of a mutant ER with an alanine in place of Ser118. Thus, the activity of the amino-terminal AF-1 of the ER is modulated by the phosphorylation of Ser118 through the Ras-MAPK cascade of the growth factor signaling pathways.

Cited by

• Identification of the Human Mnk2 Gene (MKNK2) through Protein Interaction with Estrogen Receptor β
• Direct Acetylation of the Estrogen Receptor α Hinge Region by p300 Regulates Transactivation and Hormone Sensitivity
• Mechanisms of Estrogen Action
• Estrogenic hormone action in the heart: regulatory network and function
• Ligand-independent activation of oestrogen receptor α by caveolin-1
• Nuclear receptor modulation – Role of coregulators in selective estrogen receptor modulator (SERM) actions
• Formation of an hERα–COUP‐TFI complex enhances hERα AF‐1 through Ser118 phosphorylation by MAPK
• Functional Analysis of a Novel Estrogen Receptor-β Isoform
• ERβ: Identification and characterization of a novel human estrogen receptor
• Isoforms of steroid receptor co‐activator 1 differ in their ability to potentiate transcription by the oestrogen receptor
• Tamoxifen-Bound Estrogen Receptor (ER) Strongly Interacts with the Nuclear Matrix Protein HET/SAF-B, a Novel Inhibitor of ER-Mediated Transactivation
• The Agonist Activity of Tamoxifen Is Inhibited by the Short Heterodimer Partner Orphan Nuclear Receptor in Human Endometrial Cancer Cells
• Toremifene – a promising therapy for the prevention of prostate cancer and complications of androgen deprivation therapy
• Connections and Regulation of the Human Estrogen Receptor
• Estrogen Receptor Alpha in Human Breast Cancer: Occurrence and Significance
• Estrogen receptor phosphorylation
• The Structural Basis of Estrogen Receptor/Coactivator Recognition and the Antagonism of This Interaction by Tamoxifen
• Role of Estrogen Receptor Beta in Estrogen Action
• CDK-Independent Activation of Estrogen Receptor by Cyclin D1
• Estrogen Receptors: Their Actions and Functional Roles in Health and Disease
• Estrogen receptor [wikipedia]