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Am J Physiol Regul Integr Comp Physiol 290: R1672-R1682, 2006. First published January 19, 2006; doi:10.1152/ajpregu.00239.2005
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DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

Ankyrin repeat and SOCS box protein 15 regulates protein synthesis in skeletal muscle

T. G. McDaneld,1 K. Hannon,2 and D. E. Moody1

1Department of Animal Sciences and 2Department of Basic Medical Sciences, Purdue University, West Lafayette, Indiana

Submitted 7 April 2005 ; accepted in final form 11 January 2006

Ankyrin repeat and SOCS box protein 15 (ASB15) is an Asb family member expressed predominantly in skeletal muscle. We have previously reported that ASB15 mRNA abundance decreases after administration of beta-adrenergic receptor agonists. Because beta-adrenergic receptor agonists are known to stimulate muscle hypertrophy, the objective of this study was to determine whether ASB15 regulates cellular processes that contribute to muscle growth. Stable myoblast C2C12 cells expressing full-length ASB15 (ASB15-FL) and ASB15 lacking the ankyrin repeat (ASB15-Ank) or SOCS box (ASB15-SOCS) motifs were evaluated for changes in proliferation, differentiation, protein synthesis, and protein degradation. Expression of ASB15-FL caused a delay in differentiation, followed by an increase in protein synthesis of ~34% (P < 0.05). A consistent effect of ASB15 overexpression was observed in vivo, where ectopic expression of ASB15 increased skeletal muscle fiber area (P < 0.0001) after 9 days. Expression of ASB15-SOCS altered differentiation of myoblasts, resulting in detachment of cells from culture plates. Expression of ASB15-Ank increased protein degradation by 84 h of differentiation (P < 0.05), and in vivo ectopic expression of an ASB15 construct lacking both the ankyrin repeat and SOCS box motifs decreased skeletal muscle fiber area (P < 0.0001). Together, these results suggest ASB15 participates in the regulation of protein turnover and muscle cell development by stimulating protein synthesis and regulating differentiation of muscle cells. This is the first study to demonstrate a role for an Asb family member in skeletal muscle growth.

beta-adrenergic receptor agonist; protein turnover



Address for reprint requests and other correspondence: D. E. Moody, Dept. of Animal Sciences, Iowa State Univ., Ames, IA 50014 (e-mail: moodyd{at}iastate.edu)




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Role of {beta}-Adrenoceptor Signaling in Skeletal Muscle: Implications for Muscle Wasting and Disease
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[Abstract] [Full Text] [PDF]




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