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J. Biol. Chem., Vol. 282, Issue 8, 5106-5110, February 23, 2007

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Selective Control of Skeletal Muscle Differentiation by Akt1^*

From the Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, Oregon 97239

The phosphatidylinositol 3-kinase-Akt pathway plays a central role in growth, development, and metabolism in both normal and neoplastic cells. In skeletal muscle, Akt has been implicated in regulating regeneration and hypertrophy and in counteracting atrophy. Here we provide evidence that Akt1 and not Akt2 is essential for muscle differentiation. Using a robust model of MyoD-mediated muscle development, in which dominant-negative Akt blocked differentiation, we show that targeted loss of Akt1 was equally inhibitory. Selective elimination of Akt1 had no effect on myoblast viability or proliferation but prevented differentiation by impairing the transcriptional actions of MyoD. In contrast, knockdown of Akt2 had no effect on myoblast survival or differentiation and minimally inhibited MyoD-regulated transcription. Our results define isoform-specific Akt-regulated signaling pathways in muscle cells that act through Akt1 to sustain muscle gene activation and promote differentiation.

Received for publication, December 20, 2006 , and in revised form, January 10, 2007.

^* These studies were supported by National Institutes of Health Grant RO1 DK42748 to (P. R.). 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.

The on-line version of this article (available at http://www.jbc.org) contains a supplemental figure.

¹ To whom correspondence should be addressed: Dept. of Biochemistry and Molecular Biology, Oregon Health and Science University, 3181 SW Sam Jackson Rd., Mail code L224, Portland, OR 97239. Tel.: 503-494-0536; Fax: 503-494-8393; E-mail: rotweinp{at}ohsu.edu.

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