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Science 1 December 1995:
Vol. 270. no. 5241, pp. 1491 - 1494
DOI: 10.1126/science.270.5241.1491
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Reports

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

Shigeaki Kato,  Hideki Endoh,  Yoshikazu Masuhiro,  Takuya Kitamoto,  Shimami Uchiyama,  Haruna Sasaki,  Shoichi Masushige,  Yukiko Gotoh,  Eisuke Nishida,  Hiroyuki Kawashima,  Daniel Metzger,  Pierre Chambon (1)

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 Ser 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 Ser. Thus, the activity of the amino-terminal AF-1 of the ER is modulated by the phosphorylation of Ser through the Ras-MAPK cascade of the growth factor signaling pathways.


S. Kato, Y. Masuhiro, T. Kitamoto, S. Uchiyama, H. Sasaki, S. Masushige, Department of Agricultural Chemistry, Tokyo University of Agriculture, Setagayaku, Tokyo 156, Japan.
H. Endoh and H. Kawashima, Molecular Medicine Research Laboratory II, Yamanouchi Institute for Drug Discovery Research Co. Ltd., Tsukuba, Ibaraki 305, Japan.
Y. Gotoh and E. Nishida, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606, Japan.
D. Metzger and P. Chambon, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique (CNRS)/Institut National de la Santé et de la Recherche Médicale (INSERM)/Université Louis Pasteur/Collège de France, BP163-67404 Illkirch Cedex, Communauté Urbaine de Strasbourg, France.
(1) To whom correspondence should be addressed.


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J. Mol. Endocrinol. 35, 449-464
   Abstract »    Full Text »    PDF »
Estrogenic Activities in Rodent Estrogen-Free Diets.
P. Ciana, A. Brena, P. Sparaciari, E. Bonetti, D. Di Lorenzo, and A. Maggi (2005)
Endocrinology 146, 5144-5150
   Abstract »    Full Text »    PDF »
Human Expanded Polyglutamine Androgen Receptor Mutants in Neurodegeneration as a Novel Ligand Target.
T. Furutani, K.-i. Takeyama, M. Tanabe, H. Koutoku, S. Ito, N. Taniguchi, E. Suzuki, M. Kudoh, M. Shibasaki, H. Shikama, et al. (2005)
J. Pharmacol. Exp. Ther. 315, 545-552
   Abstract »    Full Text »    PDF »
Estrogen Negatively Regulates Epidermal Growth Factor (EGF)-Mediated Signal Transducer and Activator of Transcription 5 Signaling in Human EGF Family Receptor-Overexpressing Breast Cancer Cells.
J. L. Boerner, M. A. Gibson, E. M. Fox, E. D. Posner, S. J. Parsons, C. M. Silva, and M. A. Shupnik (2005)
Mol. Endocrinol. 19, 2660-2670
   Abstract »    Full Text »    PDF »
Biology of Progesterone Receptor Loss in Breast Cancer and Its Implications for Endocrine Therapy.
X. Cui, R. Schiff, G. Arpino, C. K. Osborne, and A. V. Lee (2005)
J. Clin. Oncol. 23, 7721-7735
   Abstract »    Full Text »    PDF »
Analogs of GnRH-I and GnRH-II inhibit epidermal growth factor-induced signal transduction and resensitize resistant human breast cancer cells to 4OH-tamoxifen.
A. R Gunthert, C. Grundker, A. Olota, J. Lasche, N. Eicke, and G. Emons (2005)
Eur. J. Endocrinol. 153, 613-625
   Abstract »    Full Text »    PDF »
The p160 family coactivators regulate breast cancer cell proliferation and invasion through autocrine/paracrine activity of SDF-1{alpha}/CXCL12.
H. Kishimoto, Z. Wang, P. Bhat-Nakshatri, D. Chang, R. Clarke, and H. Nakshatri (2005)
Carcinogenesis 26, 1706-1715
   Abstract »    Full Text »    PDF »
Glycogen Synthase Kinase-3 Interacts with and Phosphorylates Estrogen Receptor {alpha} and Is Involved in the Regulation of Receptor Activity.
S. Medunjanin, A. Hermani, B. De Servi, J. Grisouard, G. Rincke, and D. Mayer (2005)
J. Biol. Chem. 280, 33006-33014
   Abstract »    Full Text »    PDF »
Rapid Estrogen-Induced Phosphorylation of the SRC-3 Coactivator Occurs in an Extranuclear Complex Containing Estrogen Receptor.
F. F. Zheng, R.-C. Wu, C. L. Smith, and B. W. O'Malley (2005)
Mol. Cell. Biol. 25, 8273-8284
   Abstract »    Full Text »    PDF »
Trastuzumab Therapy for Tamoxifen-Stimulated Endometrial Cancer.
C. Osipo, K. Meeke, H. Liu, D. Cheng, S. Lim, A. Weichel, and V. C. Jordan (2005)
Cancer Res. 65, 8504-8513
   Abstract »    Full Text »    PDF »
The mechanisms and managements of hormone-therapy resistance in breast and prostate cancers.
K-M Rau, H-Y Kang, T-L Cha, S A Miller, and M-C Hung (2005)
Endocr. Relat. Cancer 12, 511-532
   Abstract »    Full Text »    PDF »
Functional Implications of Altered Subcellular Localization of PELP1 in Breast Cancer Cells.
R. K. Vadlamudi, B. Manavathi, S. Balasenthil, S. S. Nair, Z. Yang, A. A. Sahin, and R. Kumar (2005)
Cancer Res. 65, 7724-7732
   Abstract »    Full Text »    PDF »
Growth Factors Change Nuclear Distribution of Estrogen Receptor-{alpha} via Mitogen-Activated Protein Kinase or Phosphatidylinositol 3-Kinase Cascade in a Human Breast Cancer Cell Line.
T. Takahashi, M. Ohmichi, J. Kawagoe, C. Ohshima, M. Doshida, T. Ohta, M. Saitoh, A. Mori-Abe, B. Du, H. Igarashi, et al. (2005)
Endocrinology 146, 4082-4089
   Abstract »    Full Text »    PDF »
Integration of the Extranuclear and Nuclear Actions of Estrogen.
E. R. Levin (2005)
Mol. Endocrinol. 19, 1951-1959
   Abstract »    Full Text »    PDF »
Study of Androgen Receptor Functions by Genetic Models.
T. Matsumoto, K.-i. Takeyama, T. Sato, and S. Kato (2005)
J. Biochem. 138, 105-110
   Abstract »    Full Text »    PDF »
Dysregulation of the Peroxisome Proliferator-Activated Receptor Target Genes by XPD Mutations.
E. Compe, P. Drane, C. Laurent, K. Diderich, C. Braun, J. H. J. Hoeijmakers, and J.-M. Egly (2005)
Mol. Cell. Biol. 25, 6065-6076
   Abstract »    Full Text »    PDF »
Differential Regulation of Estrogen-Inducible Proteolysis and Transcription by the Estrogen Receptor {alpha} N Terminus.
C. C. Valley, R. Metivier, N. M. Solodin, A. M. Fowler, M. T. Mashek, L. Hill, and E. T. Alarid (2005)
Mol. Cell. Biol. 25, 5417-5428
   Abstract »    Full Text »    PDF »
Histone Acetyltransferase Activity of p300 Is Required for Transcriptional Repression by the Promyelocytic Leukemia Zinc Finger Protein.
F. Guidez, L. Howell, M. Isalan, M. Cebrat, R. M. Alani, S. Ivins, I. Hormaeche, M. J. McConnell, S. Pierce, P. A. Cole, et al. (2005)
Mol. Cell. Biol. 25, 5552-5566
   Abstract »    Full Text »    PDF »
Human Mineralocorticoid Receptor Expression Renders Cells Responsive for Nongenotropic Aldosterone Actions.
C. Grossmann, A. Benesic, A. W. Krug, R. Freudinger, S. Mildenberger, B. Gassner, and M. Gekle (2005)
Mol. Endocrinol. 19, 1697-1710
   Abstract »    Full Text »    PDF »
Can Molecular Markers Predict When to Implement Treatment with Aromatase Inhibitors in Invasive Breast Cancer?.
S. Tovey, B. Dunne, C. J. Witton, A. Forsyth, T. G. Cooke, and J. M.S. Bartlett (2005)
Clin. Cancer Res. 11, 4835-4842
   Abstract »    Full Text »    PDF »
Downstream targets of growth factor and oestrogen signalling and endocrine resistance: the potential roles of c-Myc, cyclin D1 and cyclin E.
A. J Butt, C. M McNeil, E. A Musgrove, and R. L Sutherland (2005)
Endocr. Relat. Cancer 12, S47-S59
   Abstract »    Full Text »    PDF »
Splicing potentiation by growth factor signals via estrogen receptor phosphorylation.
Y. Masuhiro, Y. Mezaki, M. Sakari, K.-i. Takeyama, T. Yoshida, K. Inoue, J. Yanagisawa, S. Hanazawa, B. W. O'Malley, and S. Kato (2005)
PNAS 102, 8126-8131
   Abstract »    Full Text »    PDF »
The Nuclear Receptor Superfamily: A Personal Retrospect on the First Two Decades.
P. Chambon (2005)
Mol. Endocrinol. 19, 1418-1428
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Tumor-Stromal Interaction through the Estrogen-Signaling Pathway in Human Breast Cancer.
Y. Yamaguchi, H. Takei, K. Suemasu, Y. Kobayashi, M. Kurosumi, N. Harada, and S.-i. Hayashi (2005)
Cancer Res. 65, 4653-4662
   Abstract »    Full Text »    PDF »


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