Estrogen receptor phosphorylation

doi:10.1016/S0039-128X(02)00110-1

Steroids

Volume 68, Issue 1, January 2003, Pages 1-9

https://doi.org/10.1016/S0039-128X(02)00110-1 Get rights and content

Abstract

Estrogen receptor α (ERα) is phosphorylated on multiple amino acid residues. For example, in response to estradiol binding, human ERα is predominately phosphorylated on Ser-118 and to a lesser extent on Ser-104 and Ser-106. In response to activation of the mitogen-activated protein kinase pathway, phosphorylation occurs on Ser-118 and Ser-167. These serine residues are all located within the activation function 1 region of the N-terminal domain of ERα. In contrast, activation of protein kinase A increases the phosphorylation of Ser-236, which is located in the DNA-binding domain. The in vivo phosphorylation status of Tyr-537, located in the ligand-binding domain, remains controversial. In this review, I present evidence that these phosphorylations occur, and identify the kinases thought to be responsible. Additionally, the functional importance of ERα phosphorylation is discussed.

Section snippets

Overview

This review will focus on the major phosphorylation sites in estrogen receptor α (ERα) that occur in response to either estradiol or through the activation of second messenger signaling pathways. The following questions will be addressed: (1) What are the sites of ER phosphorylation and which kinases are responsible for these phosphorylations? (2) How does phosphorylation influence ER function? (3) What is known about ER phosphatases? (4) How does estradiol directly influence signal

Acknowledgements

I thank Margaret Shupnik for helpful discussions and critical reading of the manuscript. This work was supported by Research Project Grant #TBE-97523 from the American Cancer Society.

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ReviewEstrogen receptor phosphorylation

Abstract

Section snippets

Overview

Acknowledgements

Cell

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Semin. Perinatol.

Gynecol. Oncol.

Steroids

Mol. Cell. Biol. Res. Commun.

Exp. Hematol.

Cell

Steroids

Cell

Cell

Cell

J. Biol. Chem.

J. Steroid Biochem. Mol. Biol.

J. Biol. Chem.

J. Biol. Chem.

Mol. Cell

J. Steroid Biochem. Mol. Biol.

Mol. Cell. Endocrinol.

J. Steroid Biochem. Mol. Biol.

Mol. Cell

J. Biol. Chem.

J. Biol. Chem.

J. Steroid Biochem. Mol. Biol.

Cell

J. Biol. Chem.

Dopaminergic and ligand-independent activation of steroid hormone receptors

Science

Coupling of dual signaling pathways: epidermal growth factor action involves the estrogen receptor

Proc. Natl. Acad. Sci. U.S.A.

Stimulation of estrogen receptor-mediated transcription and alteration in the phosphorylation state of the rat uterine estrogen receptor by estrogen, cyclic adenosine monophosphate, and insulin-like growth factor-1

Mol. Endocrinol.

Synergistic activation of estrogen receptor-mediated transcription by estradiol and protein kinase activators

Mol. Endocrinol.

Modulation of the ligand-independent activation of the human estrogen receptor by hormone and antihormone

Proc. Natl. Acad. Sci. U.S.A.

Peptide growth factors elicit estrogen receptor-dependent transcriptional activation of an estrogen-responsive element

Mol. Endocrinol.

Activation of transcriptionally inactive human estrogen receptors by cyclic adenosine 3′,5′-monophosphate and ligands including antiestrogens

Mol. Endocrinol.

Estrogen action via the cAMP signaling pathway: stimulation of adenylate cyclase and cAMP-regulated gene transcription

Proc. Natl. Acad. Sci. U.S.A.

Peptide growth factor cross-talk with the estrogen receptor requires the A/B domain and occurs independently of protein kinase C or estradiol

Endocrinology

Activation of the unliganded estrogen receptor by EGF involves the MAP kinase pathway and direct phosphorylation

EMBO J.

Physiological coupling of growth factor and steroid receptor signaling pathways: estrogen receptor knockout mice lack estrogen-like response to epidermal growth factor

Proc. Natl. Acad. Sci. U.S.A.

Ligand-independent activation of pituitary ER: dependence on PKA-stimulated pathways

Endocrinology

Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta

Endocrinology

Estrogen receptors: selective ligands, partners, and distinctive pharmacology

Recent Prog. Horm. Res.

Estrogen receptor variants

J. Mammary Gland Biol. Neoplasia

Selective expression of estrogen receptor alpha and beta isoforms in human pituitary tumors

J. Clin. Endocrinol. Metab.

Differential expression and regulation of estrogen receptors (ERs) in rat pituitary and cell lines: estrogen decreases ERalpha protein and estrogen responsiveness

Endocrinology

Identification of two transactivation domains in the mouse oestrogen receptor

Nucleic Acids Res.

The estrogen-dependent c-JunER protein causes a reversible loss of mammary epithelial cell polarity involving a destabilization of adherens junctions

J. Cell Biol.

A modified oestrogen receptor ligand-binding domain as an improved switch for the regulation of heterologous proteins

Nucleic Acids Res.

Ligand-dependent, transcriptionally productive association of the amino-and carboxyl-terminal regions of a steroid hormone nuclear receptor

Proc. Natl. Acad. Sci. U.S.A.

Human estrogen receptor transactivational capacity is determined by both cellular and promoter context and mediated by two functionally distinct intramolecular regions

Mol. Endocrinol.

Review
Estrogen receptor phosphorylation