Molecular Endocrinology, Vol 8, 182-188, Copyright © 1994 by Endocrine Society

ARTICLES

Characterization of ligand-dependent phosphorylation of the estrogen receptor

H Lahooti, R White, PS Danielian and MG Parker
Molecular Endocrinology Laboratory, Imperial Cancer Research Fund, London, United Kingdom.

The mouse estrogen receptor is phosphorylated upon estrogen binding at multiple serine residues located mainly between residues 121 and 599. Phosphorylation is progressively reduced in mutant receptors that are defective in estrogen- and DNA-binding activities, suggesting that it occurs in stages, initially as a consequence of hormone binding and subsequently after DNA binding. Phosphopeptide maps of the receptor expressed in the presence of estrogen or 4-hydroxytamoxifen are similar, suggesting that the effects of this antiestrogen on transcriptional activity are not mediated by differences in phosphorylation. Although it is unclear whether phosphorylation is a prerequisite for transcriptional activity, the similarity in the phosphopeptide maps of the wild-type receptor and the transcriptionally defective mutant confirm that phosphorylation does not occur simply as a consequence of estrogen-dependent transcriptional activation.

This article has been cited by other articles:

				J. Cheng, C. Zhang, and D. J. Shapiro A Functional Serine 118 Phosphorylation Site in Estrogen Receptor-{alpha} Is Required for Down-Regulation of Gene Expression by 17{beta}-Estradiol and 4-Hydroxytamoxifen Endocrinology, October 1, 2007; 148(10): 4634 - 4641. [Abstract] [Full Text] [PDF]

				M. P.V. Shekhar, S. Santner, K. A. Carolin, and L. Tait Direct Involvement of Breast Tumor Fibroblasts in the Modulation of Tamoxifen Sensitivity Am. J. Pathol., May 1, 2007; 170(5): 1546 - 1560. [Abstract] [Full Text] [PDF]

				J. M. Garcia-Pedrero, E. Kiskinis, M. G. Parker, and B. Belandia The SWI/SNF Chromatin Remodeling Subunit BAF57 Is a Critical Regulator of Estrogen Receptor Function in Breast Cancer Cells J. Biol. Chem., August 11, 2006; 281(32): 22656 - 22664. [Abstract] [Full Text] [PDF]

				S. Glaros, N. Atanaskova, C. Zhao, D. F. Skafar, and K. B. Reddy Activation Function-1 Domain of Estrogen Receptor Regulates the Agonistic and Antagonistic Actions of Tamoxifen Mol. Endocrinol., May 1, 2006; 20(5): 996 - 1008. [Abstract] [Full Text] [PDF]

				Y. M. Shah and B. G. Rowan The Src Kinase Pathway Promotes Tamoxifen Agonist Action in Ishikawa Endometrial Cells through Phosphorylation-Dependent Stabilization of Estrogen Receptor {alpha} Promoter Interaction and Elevated Steroid Receptor Coactivator 1 Activity Mol. Endocrinol., March 1, 2005; 19(3): 732 - 748. [Abstract] [Full Text] [PDF]

				P. Ciana, S. Ghisletti, P. Mussi, I. Eberini, E. Vegeto, and A. Maggi Estrogen Receptor {alpha}, a Molecular Switch Converting Transforming Growth Factor-{alpha}-mediated Proliferation into Differentiation in Neuroblastoma Cells J. Biol. Chem., August 22, 2003; 278(34): 31737 - 31744. [Abstract] [Full Text] [PDF]

				L. Bjornstrom and M. Sjoberg Mutations in the Estrogen Receptor DNA-binding Domain Discriminate between the Classical Mechanism of Action and Cross-talk with Stat5b and Activating Protein 1 (AP-1) J. Biol. Chem., December 6, 2002; 277(50): 48479 - 48483. [Abstract] [Full Text] [PDF]

				L. Bjornstrom and M. Sjoberg Signal Transducers and Activators of Transcription as Downstream Targets of Nongenomic Estrogen Receptor Actions Mol. Endocrinol., October 1, 2002; 16(10): 2202 - 2214. [Abstract] [Full Text] [PDF]

				P. Hatzis and I. Talianidis Regulatory Mechanisms Controlling Human Hepatocyte Nuclear Factor 4{alpha} Gene Expression Mol. Cell. Biol., November 1, 2001; 21(21): 7320 - 7330. [Abstract] [Full Text] [PDF]

				S. Nilsson, S. Makela, E. Treuter, M. Tujague, J. Thomsen, G. Andersson, E. Enmark, K. Pettersson, M. Warner, and J.-A. Gustafsson Mechanisms of Estrogen Action Physiol Rev, October 1, 2001; 81(4): 1535 - 1565. [Abstract] [Full Text] [PDF]

				E. M. Apostolakis, J. Garai, J. E. Lohmann, J. H. Clark, and B. W. O’Malley Epidermal Growth Factor Activates Reproductive Behavior Independent of Ovarian Steroids in Female Rodents Mol. Endocrinol., July 1, 2000; 14(7): 1086 - 1098. [Abstract] [Full Text]

				P. Webb, P. Nguyen, C. Valentine, G. N. Lopez, G. R. Kwok, E. McInerney, B. S. Katzenellenbogen, E. Enmark, J.-A. Gustafsson, S. Nilsson, et al. The Estrogen Receptor Enhances AP-1 Activity by Two Distinct Mechanisms with Different Requirements for Receptor Transactivation Functions Mol. Endocrinol., October 1, 1999; 13(10): 1672 - 1685. [Abstract] [Full Text]

				P. Webb, P. Nguyen, J. Shinsako, C. Anderson, W. Feng, M. P. Nguyen, D. Chen, S.-M. Huang, S. Subramanian, E. McKinerney, et al. Estrogen Receptor Activation Function 1 Works by Binding p160 Coactivator Proteins Mol. Endocrinol., October 1, 1998; 12(10): 1605 - 1618. [Abstract] [Full Text]

				C. Patrone, E. Gianazza, S. Santagati, P. Agrati, and A. Maggi Divergent Pathways Regulate Ligand-Independent Activation of ER{alpha} in SK-N-BE Neuroblastoma and COS-1 Renal Carcinoma Cells Mol. Endocrinol., June 1, 1998; 12(6): 835 - 841. [Abstract] [Full Text]

				J. I. Macgregor and V. C. Jordan Basic Guide to the Mechanisms of Antiestrogen Action Pharmacol. Rev., June 1, 1998; 50(2): 151 - 196. [Abstract] [Full Text] [PDF]

				M. von Lindern, L. Boer, O. Wessely, M. Parker, and H. Beug The Transactivation Domain AF-2 but Not the DNA-Binding Domain of the Estrogen Receptor Is Required to Inhibit Differentiation of Avian Erythroid Progenitors Mol. Endocrinol., February 1, 1998; 12(2): 263 - 277. [Abstract] [Full Text]

				G. B. Tremblay, A. Tremblay, N. G. Copeland, D. J. Gilbert, N. A. Jenkins, F. Labrie, and V. Giguère Cloning, Chromosomal Localization, and Functional Analysis of the Murine Estrogen Receptor {beta} Mol. Endocrinol., March 1, 1997; 11(3): 353 - 365. [Abstract] [Full Text]

				M.-S. Jiang and G. W. Hart A Subpopulation of Estrogen Receptors Are Modified by O-Linked N-Acetylglucosamine J. Biol. Chem., January 24, 1997; 272(4): 2421 - 2428. [Abstract] [Full Text] [PDF]

				Y. Kobayashi, T. Kitamoto, Y. Masuhiro, M. Watanabe, T. Kase, D. Metzger, J. Yanagisawa, and S. Kato p300 Mediates Functional Synergism between AF-1 and AF-2 of Estrogen Receptor alpha and beta by Interacting Directly with the N-terminal A/B Domains J. Biol. Chem., May 19, 2000; 275(21): 15645 - 15651. [Abstract] [Full Text] [PDF]

				J. E. Valentine, E. Kalkhoven, R. White, S. Hoare, and M. G. Parker Mutations in the Estrogen Receptor Ligand Binding Domain Discriminate between Hormone-dependent Transactivation and Transrepression J. Biol. Chem., August 11, 2000; 275(33): 25322 - 25329. [Abstract] [Full Text] [PDF]