This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Blagden, C. S.
Right arrow Articles by Burden, S. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Blagden, C. S.
Right arrow Articles by Burden, S. J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, March 2004, p. 1983-1989, Vol. 24, No. 5
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.5.1983-1989.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Accelerated Response of the myogenin Gene to Denervation in Mutant Mice Lacking Phosphorylation of Myogenin at Threonine 87

Chris S. Blagden, Larry Fromm,{dagger} and Steven J. Burden*

Molecular Neurobiology Program, Skirball Institute of Biomolecular Medicine, New York University Medical School, New York, New York 10016

Received 24 October 2003/ Returned for modification 23 November 2003/ Accepted 3 December 2003

Gene expression in skeletal muscle is regulated by a family of myogenic basic helix-loop-helix (bHLH) proteins. The binding of these bHLH proteins, notably MyoD and myogenin, to E-boxes in their own regulatory regions is blocked by protein kinase C (PKC)-mediated phosphorylation of a single threonine residue in their basic region. Because electrical stimulation increases PKC activity in skeletal muscle, these data have led to an attractive model suggesting that electrical activity suppresses gene expression by stimulating phosphorylation of this critical threonine residue in myogenic bHLH proteins. We show that electrical activity stimulates phosphorylation of myogenin at threonine 87 (T87) in vivo and that calmodulin-dependent kinase II (CaMKII), as well as PKC, catalyzes this reaction in vitro. We find that phosphorylation of myogenin at T87 is dispensable for skeletal muscle development. We show, however, that the decrease in myogenin (myg) expression following innervation is delayed and that the increase in expression following denervation is accelerated in mutant mice lacking phosphorylation of myogenin at T87. These data indicate that two distinct innervation-dependent mechanisms restrain myogenin activity: an inactivation mechanism mediated by phosphorylation of myogenin at T87, and a second, novel regulatory mechanism that regulates myg gene activity independently of T87 phosphorylation.

* Corresponding author. Mailing address: Molecular Neurobiology Program, Skirball Institute of Biomolecular Medicine, New York University Medical School, 540 First Ave., New York, NY 10016. Phone: (212) 263-7341. Fax: (212) 263-2842. E-mail: burden{at}saturn.med.nyu.edu.

{dagger} Present address: Center for Medical Education, Ball State University, Muncie, IN 47303-4609.

Molecular and Cellular Biology, March 2004, p. 1983-1989, Vol. 24, No. 5
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.5.1983-1989.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Berghella, L., De Angelis, L., De Buysscher, T., Mortazavi, A., Biressi, S., Forcales, S. V., Sirabella, D., Cossu, G., Wold, B. J. (2008). A highly conserved molecular switch binds MSY-3 to regulate myogenin repression in postnatal muscle. Genes Dev. 22: 2125-2138 [Abstract] [Full Text]  
  • Ekmark, M., Rana, Z. A., Stewart, G., Hardie, D. G., Gundersen, K. (2007). De-phosphorylation of MyoD is linking nerve-evoked activity to fast myosin heavy chain expression in rodent adult skeletal muscle. J. Physiol. 584: 637-650 [Abstract] [Full Text]  
  • Wang, X., Blagden, C., Fan, J., Nowak, S. J., Taniuchi, I., Littman, D. R., Burden, S. J. (2005). Runx1 prevents wasting, myofibrillar disorganization, and autophagy of skeletal muscle. Genes Dev. 19: 1715-1722 [Abstract] [Full Text]  
  • Kim, C.-H., Xiong, W. C., Mei, L. (2005). Inhibition of MuSK Expression by CREB Interacting with a CRE-Like Element and MyoD. Mol. Cell. Biol. 25: 5329-5338 [Abstract] [Full Text]  
  • Vinals, F., Ventura, F. (2004). Myogenin Protein Stability Is Decreased by BMP-2 through a Mechanism Implicating Id1. J. Biol. Chem. 279: 45766-45772 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»