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

J. Biol. Chem., Vol. 282, Issue 50, 36303-36313, December 14, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/50/36303    most recent M707287200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Soundararajan, R. Articles by Pearce, D. Search for Related Content PubMed PubMed Citation Articles by Soundararajan, R. Articles by Pearce, D. Social Bookmarking                      What's this?

Differential Activities of Glucocorticoid-induced Leucine Zipper Protein Isoforms^*

Rama Soundararajan¹, Jian Wang, Daniël Melters, and David Pearce²

From the Division of Nephrology, Department of Medicine, University of California, San Francisco, California 94143-0532 and the Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94143

Glucocorticoid-induced leucine zipper protein (GILZ) is expressed in both epithelial and immune tissues and modulates a variety of cellular functions, including proliferation and epithelial sodium channel (ENaC) activity. A number of reports have described various GILZ activities, focusing on a single isoform with molecular mass of 17 kDa, now termed GILZ1. In GILZ immunoblots using a newly developed antiserum, we detected multiple species in extracts from cultured kidney cells. Mass spectrometric analysis revealed that one of these represented a previously uncharacterized distinct isoform of GILZ, GILZ2. Rapid amplification of cDNA ends was used to clone cDNAs corresponding to four isoforms, which, in addition to GILZ1 and GILZ2, included new isoforms GILZ3 and GILZ4. Heterologous expression of these four GILZ isoforms in cultured cells revealed striking functional differences. Notably, GILZ1 was the only isoform that significantly stimulated ENaC-mediated Na⁺ current in a kidney collecting duct cell line, although GILZ2 and GILZ3 also stimulated ENaC surface expression in HEK 293 cells. GILZ1 and GILZ3, and to a lesser extent GILZ2, inhibited ERK phosphorylation. Interestingly, GILZ4, which had no effect on either ENaC or ERK, potently suppressed cellular proliferation, as did GILZ1, but not GILZ2 or GILZ3. Finally, rat and mouse tissues all expressed multiple GILZ species but varied in the relative abundance of each. These data suggest that multiple GILZ isoforms are expressed in most cells and tissues and that these play distinct roles in regulating key cellular functions, including proliferation and ion transport. Furthermore, GILZ inhibition of ERK appears to play an essential role in stimulation of cell surface ENaC but not in inhibition of proliferation.

Received for publication, August 30, 2007 , and in revised form, October 15, 2007.

^* This work is supported by National Institutes of Health Grants R01-DK51151 (to D. P.) and K01-DK078679-01 (to R. S.). 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.

¹ Supported by a postdoctoral fellowship grant from the American Heart Association (Western States Affiliate).

² To whom correspondence should be addressed: 600 16th St., Rm. N274H-Genentech Hall-Mission Bay Campus, Box 2140, University of California, San Francisco, CA 94107-2140. Tel.: 415-476-7015; Fax: 415-502-8644; E-mail: dpearce{at}medsfgh.ucsf.edu.

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

This article has been cited by other articles:

				M. Gallacher, S. G. Brown, B. G. Hale, R. Fearns, R. E. Olver, R. E. Randall, and S. M. Wilson Cation currents in human airway epithelial cells induced by infection with influenza A virus J. Physiol., July 1, 2009; 587(13): 3159 - 3173. [Abstract] [Full Text] [PDF]

				R. Soundararajan, D. Melters, I-C. Shih, J. Wang, and D. Pearce Epithelial sodium channel regulated by differential composition of a signaling complex PNAS, May 12, 2009; 106(19): 7804 - 7809. [Abstract] [Full Text] [PDF]

				K. De Bosscher and G. Haegeman Minireview: Latest Perspectives on Antiinflammatory Actions of Glucocorticoids Mol. Endocrinol., March 1, 2009; 23(3): 281 - 291. [Abstract] [Full Text] [PDF]

				M. B. Butterworth, R. S. Edinger, R. A. Frizzell, and J. P. Johnson Regulation of the epithelial sodium channel by membrane trafficking Am J Physiol Renal Physiol, January 1, 2009; 296(1): F10 - F24. [Abstract] [Full Text] [PDF]

				S. de Seigneux, V. Leroy, H. Ghzili, M. Rousselot, S. Nielsen, B. C. Rossier, P.-Y. Martin, and E. Feraille NF-{kappa}B Inhibits Sodium Transport via Down-regulation of SGK1 in Renal Collecting Duct Principal Cells J. Biol. Chem., September 12, 2008; 283(37): 25671 - 25681. [Abstract] [Full Text] [PDF]