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

J. Biol. Chem., Vol. 281, Issue 8, 5277-5287, February 24, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/8/5277    most recent M510004200v1 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 Ku, M. Articles by Hata, A. Search for Related Content PubMed PubMed Citation Articles by Ku, M. Articles by Hata, A. Social Bookmarking                      What's this?

OAZ Regulates Bone Morphogenetic Protein Signaling through Smad6 Activation^*

Manching Ku, Shavonne Howard, Weihua Ni, Giorgio Lagna, and Akiko Hata¹

From the Molecular Cardiology Research Institute, Tufts-New England Medical Center and the Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 02111

The intensity and duration of activation of a signal transduction system are important determinants of the specificity of the cellular response to the stimulus. It is unclear how different cells can generate a signal of varying intensity and duration in response to the same cytokine. We investigated the role of the transcriptional activator and Smad1/4 cofactor OAZ in regulating bone morphogenetic protein (BMP) signaling. We demonstrate that upon BMP4 stimulation, an OAZ-Smad1/4 complex binds to and activates the gene encoding Smad6, a specific inhibitor of the BMP pathway. Removal of endogenous OAZ from pluripotent embryonal carcinoma cells prevents the induction of Smad6 by BMP4 and extends the period of detection of phosphorylated Smad1 after BMP stimulation. Conversely, in cells that do not normally express OAZ, such as myoblasts and smooth muscle cells, forced OAZ expression leads to faster and higher Smad6 induction in response to BMP4, decrease of Smad1 phosphorylation, and attenuation of BMP-mediated responses. Our results demonstrate that OAZ can alter the intensity and duration of the BMP stimulus through Smad6 and indicate that the tissue-specific expression of OAZ is a critical determinant of the cellular response to the BMP signal.

Received for publication, September 12, 2005 , and in revised form, December 20, 2005.

^* This study was supported by grants from the National Institutes of Health and the American Cancer Society (to A. H.). 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 To whom correspondence should be addressed: Molecular Cardiology Research Institute, Tufts-New England Medical Center, 750 Washington St., Box 8486, Boston, MA 02111. Tel.: 617-636-0614; Fax: 617-636-5649; E-mail: akiko.hata{at}tufts.edu.

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

This article has been cited by other articles:

				W. A. Alcaraz, D. A. Gold, E. Raponi, P. M. Gent, D. Concepcion, and B. A. Hamilton Zfp423 controls proliferation and differentiation of neural precursors in cerebellar vermis formation PNAS, December 19, 2006; 103(51): 19424 - 19429. [Abstract] [Full Text] [PDF]

				G. Lagna, P. H. Nguyen, W. Ni, and A. Hata BMP-dependent activation of caspase-9 and caspase-8 mediates apoptosis in pulmonary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L1059 - L1067. [Abstract] [Full Text] [PDF]