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

This Article Full Text Full Text (PDF) All Versions of this Article: 289/4/C853    most recent 00093.2005v1 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 ISI Web of Science 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 ISI Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Armstrong, D. D. Articles by Esser, K. A. Search for Related Content PubMed PubMed Citation Articles by Armstrong, D. D. Articles by Esser, K. A.

RECEPTORS AND SIGNAL TRANSDUCTION

Wnt/-catenin signaling activates growth-control genes during overload-induced skeletal muscle hypertrophy

¹University of Illinois Chicago, School of Kinesiology, Chicago, Illinois; and ²University of Kentucky, Department of Physiology, Lexington, Kentucky

Submitted 3 March 2005 ; accepted in final form 8 May 2005

-Catenin is a transcriptional activator shown to regulate the embryonic, postnatal, and oncogenic growth of many tissues. In most research to date, -catenin activation has been the unique downstream function of the Wnt signaling pathway. However, in the heart, a Wnt-independent mechanism involving Akt-mediated phosphorylation of glycogen synthase kinase (GSK)-3 was recently shown to activate -catenin and regulate cardiomyocyte growth. In this study, results have identified the activation of the Wnt/-catenin pathway during hypertrophy of mechanically overloaded skeletal muscle. Significant increases in -catenin were determined during skeletal muscle hypertrophy. In addition, the Wnt receptor, mFrizzled (mFzd)-1, the signaling mediator disheveled-1, and the transcriptional co-activator, lymphocyte enhancement factor (Lef)-1, are all increased during hypertrophy of the overloaded mouse plantaris muscle. Experiments also determined an increased association between GSK-3 and the inhibitory frequently rearranged in advanced T cell-1 protein with no increase in GSK-3 phosphorylation (Ser9). Finally, skeletal muscle overload resulted in increased nuclear -catenin/Lef-1 expression and induction of the transcriptional targets c-Myc, cyclin D1, and paired-like homeodomain transcription factor 2. Thus this study provides the first evidence that the Wnt signaling pathway induces -catenin/Lef-1 activation of growth-control genes during overload induced skeletal muscle hypertrophy.

lymphocyte enhancement factor-1; glycogen synthase kinase-3; paired like homeodomain transcription factor-2; c-Myc

This article has been cited by other articles:

				H. E. MacLean, W. S. M. Chiu, A. J. Notini, A.-M. Axell, R. A. Davey, J. F. McManus, C. Ma, D. R. Plant, G. S. Lynch, and J. D. Zajac Impaired skeletal muscle development and function in male, but not female, genomic androgen receptor knockout mice FASEB J, August 1, 2008; 22(8): 2676 - 2689. [Abstract] [Full Text] [PDF]

				J. L. J. van der Velden, R. C. J. Langen, M. C. J. M. Kelders, J. Willems, E. F. M. Wouters, Y. M. W. Janssen-Heininger, and A. M. W. J. Schols Myogenic differentiation during regrowth of atrophied skeletal muscle is associated with inactivation of GSK-3beta Am J Physiol Cell Physiol, May 1, 2007; 292(5): C1636 - C1644. [Abstract] [Full Text] [PDF]

				T. Brade, J. Manner, and M. Kuhl The role of Wnt signalling in cardiac development and tissue remodelling in the mature heart Cardiovasc Res, November 1, 2006; 72(2): 198 - 209. [Abstract] [Full Text] [PDF]

				D. D. Armstrong, V. L. Wong, and K. A. Esser Expression of beta-catenin is necessary for physiological growth of adult skeletal muscle Am J Physiol Cell Physiol, July 1, 2006; 291(1): C185 - C188. [Abstract] [Full Text] [PDF]

				P. W. Heiser, J. Lau, M. M. Taketo, P. L. Herrera, and M. Hebrok Stabilization of {beta}-catenin impacts pancreas growth Development, May 15, 2006; 133(10): 2023 - 2032. [Abstract] [Full Text] [PDF]