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Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):18117-22. Epub 2005 Dec 5.

Regulation of muscle growth by multiple ligands signaling through activin type II receptors.

Author information

  • 1Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. sjlee@jhmi.edu

Abstract

Myostatin is a secreted protein that normally functions as a negative regulator of muscle growth. Agents capable of blocking the myostatin signaling pathway could have important applications for treating human muscle degenerative diseases as well as for enhancing livestock production. Here we describe a potent myostatin inhibitor, a soluble form of the activin type IIB receptor (ACVR2B), which can cause dramatic increases in muscle mass (up to 60% in 2 weeks) when injected into wild-type mice. Furthermore, we show that the effect of the soluble receptor is attenuated but not eliminated in Mstn(-/-) mice, suggesting that at least one other ligand in addition to myostatin normally functions to limit muscle growth. Finally, we provide genetic evidence that these ligands signal through both activin type II receptors, ACVR2 and ACVR2B, to regulate muscle growth in vivo.

PMID:
16330774
[PubMed - indexed for MEDLINE]
PMCID:
PMC1306793
Free PMC Article
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