This Article Full Text Full Text (PDF) All Versions of this Article: 145/11/4991    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart 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 Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tiffin, N. Articles by Rosenthal, S. M. Search for Related Content PubMed PubMed Citation Articles by Tiffin, N. Articles by Rosenthal, S. M.

Akt Phosphorylation Is Not Sufficient for Insulin-Like Growth Factor-Stimulated Myogenin Expression but Must Be Accompanied by Down-Regulation of Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Phosphorylation

Department of Pediatrics (N.T., S.A., N.-Y.W., S.M.R.), University of California San Francisco, San Francisco, California 94143; and Cancer Research Institute (D.S.), University of California San Francisco, San Francisco, California 94115

Address all correspondence and requests for reprints to: Stephen M. Rosenthal, Department of Pediatrics, Box 0434, University of California San Francisco, San Francisco, California 94143-0434. E-mail: smr{at}itsa ucsf.edu.

IGF-I has a unique biphasic effect on skeletal muscle differentiation. Initially, IGF-I inhibits expression of myogenin, a skeletal muscle-specific regulatory factor essential for myogenesis. Subsequently, IGF-I switches to stimulating expression of myogenin. The mechanisms that mediate this switch in IGF action are incompletely understood. Several laboratories have demonstrated that the phosphatidylinositol-3-kinase/Akt signaling pathway is essential for myogenic differentiation and have suggested that this pathway mediates IGF-I stimulation of myogenin mRNA expression, an early critical step in the differentiation process. These studies, however, did not address concurrent Akt and MAPK/ERK1/2 phosphorylation, the latter of which is also known to regulate myogenic differentiation. In the present study in rat L6E9 muscle cells, we have manipulated ERK1/2 phosphorylation with either an upstream inhibitor or activator and examined concurrent levels of Akt and ERK1/2 phosphorylation and of myogenin mRNA expression in response to treatment with IGF-I. We find that even in the presence of phosphorylated Akt, it is only when ERK1/2 phosphorylation is inhibited that IGF-I can stimulate myogenin mRNA expression. Thus, although Akt phosphorylation may be necessary, it is not sufficient for induction of myogenic differentiation by IGF-I and must be accompanied by a decrease in ERK1/2 phosphorylation.

This article has been cited by other articles:

				C. De Alvaro, I. Nieto-Vazquez, J. M. Rojas, and M. Lorenzo Nuclear Exclusion of Forkhead Box O and Elk1 and Activation of Nuclear Factor-{kappa}B Are Required for C2C12-RasV12C40 Myoblast Differentiation Endocrinology, February 1, 2008; 149(2): 793 - 801. [Abstract] [Full Text] [PDF]

				V. Odemis, K. Boosmann, M. T. Dieterlen, and J. Engele The chemokine SDF1 controls multiple steps of myogenesis through atypical PKC{zeta} J. Cell Sci., November 15, 2007; 120(22): 4050 - 4059. [Abstract] [Full Text] [PDF]

				S.-E. Chen, B. Jin, and Y.-P. Li TNF-{alpha} regulates myogenesis and muscle regeneration by activating p38 MAPK Am J Physiol Cell Physiol, May 1, 2007; 292(5): C1660 - C1671. [Abstract] [Full Text] [PDF]

				V. Jacquemin, G. S. Butler-Browne, D. Furling, and V. Mouly IL-13 mediates the recruitment of reserve cells for fusion during IGF-1-induced hypertrophy of human myotubes J. Cell Sci., February 15, 2007; 120(4): 670 - 681. [Abstract] [Full Text] [PDF]

				M. Zhan, B. Jin, S.-E. Chen, J. M. Reecy, and Y.-P. Li TACE release of TNF-{alpha} mediates mechanotransduction-induced activation of p38 MAPK and myogenesis J. Cell Sci., February 15, 2007; 120(4): 692 - 701. [Abstract] [Full Text] [PDF]

				E. Edstrom, M. Altun, M. Hagglund, and B. Ulfhake Atrogin-1/MAFbx and MuRF1 Are Downregulated in Aging-Related Loss of Skeletal Muscle. J. Gerontol. A Biol. Sci. Med. Sci., July 1, 2006; 61(7): 663 - 674. [Abstract] [Full Text] [PDF]