HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 12, 7850-7855, March 24, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/12/7850    most recent M509115200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, Y.-K. Articles by Moore, D. D. Search for Related Content PubMed PubMed Citation Articles by Lee, Y.-K. Articles by Moore, D. D. Social Bookmarking                      What's this?

Phosphorylation of the Hinge Domain of the Nuclear Hormone Receptor LRH-1 Stimulates Transactivation^*

From the Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030

The nuclear receptor LRH-1 (NR5A2) functions to regulate expression of a number of genes associated with bile acid homeostasis and other liver functions, but mechanisms that modulate its activity remain unclear. We have found that mitogenic stimuli, including treatment with phorbol myristate (PMA), increase LRH-1 transactivation. This response maps to the hinge and ligand binding domains of LRH-1 and is blocked by the mitogen-activated protein kinase ERK1/2 inhibitor U0126. LRH-1 is a phosphoprotein and hinge domain serine residues at 238 and 243 are required for effective phosphorylation, both in vitro and in cells. Preventing phosphorylation of these residues by mutating both to alanine decreases PMA-dependent LRH-1 transactivation and mimicking phosphorylation by mutation to positively charged aspartate residues increases basal transactivation. Although serine phosphorylation of the hinge of SF-1 (NR5A1), the closest relative of LRH-1, confers a similar response, the specific targets differ in the two closely related orphan receptors. These results define a novel pathway for the modulation of LRH-1 transactivation and identify specific LRH-1 residues as downstream targets of mitogenic stimuli. This pathway may contribute to recently described proliferative functions of LRH-1.

Received for publication, August 18, 2005 , and in revised form, January 12, 2006.

^* This work was supported by National Institutes of Health RO1 DK068804 (to D. D. M.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

² Current address: Dept. of Molecular Genetics, University of Texas Southwestern Medical Center, Harry Hines Blvd., Dallas, TX 75390.

¹ To whom correspondence should be addressed: Dept. of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030. Tel.: 713-798-6638; Fax: 713-798-3017; E-mail: ylee{at}bcm.tmc.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				Y.-K. Lee, D. R. Schmidt, C. L. Cummins, M. Choi, L. Peng, Y. Zhang, B. Goodwin, R. E. Hammer, D. J. Mangelsdorf, and S. A. Kliewer Liver Receptor Homolog-1 Regulates Bile Acid Homeostasis but Is Not Essential for Feedback Regulation of Bile Acid Synthesis Mol. Endocrinol., June 1, 2008; 22(6): 1345 - 1356. [Abstract] [Full Text] [PDF]

				N. Venteclef, A. Haroniti, J.-J. Tousaint, I. Talianidis, and P. Delerive Regulation of Anti-atherogenic Apolipoprotein M Gene Expression by the Orphan Nuclear Receptor LRH-1 J. Biol. Chem., February 15, 2008; 283(7): 3694 - 3701. [Abstract] [Full Text] [PDF]

				T. Kanayama, M. Arito, K. So, S. Hachimura, J. Inoue, and R. Sato Interaction between Sterol Regulatory Element-binding Proteins and Liver Receptor Homolog-1 Reciprocally Suppresses Their Transcriptional Activities J. Biol. Chem., April 6, 2007; 282(14): 10290 - 10298. [Abstract] [Full Text] [PDF]

				M. Mueller, A. Atanasov, I. Cima, N. Corazza, K. Schoonjans, and T. Brunner Differential Regulation of Glucocorticoid Synthesis in Murine Intestinal Epithelial Versus Adrenocortical Cell Lines Endocrinology, March 1, 2007; 148(3): 1445 - 1453. [Abstract] [Full Text] [PDF]

				W. Zheng, J. Yang, Q. Jiang, Z. He, and L. M Halvorson Liver receptor homologue-1 regulates gonadotrope function J. Mol. Endocrinol., February 1, 2007; 38(2): 207 - 219. [Abstract] [Full Text] [PDF]