C1-Ten is a protein tyrosine phosphatase of insulin receptor substrate 1 (IRS-1), regulating IRS-1 stability and muscle atrophy

Ara Koh, Mi Nam Lee, Yong Ryoul Yang, Heeyoon Jeong, Jaewang Ghim, Jeongeun Noh, Jaeyoon Kim, Dongryeol Ryu, Sehoon Park, Parkyong Song, Seung Hoi Koo, Nick R. Leslie, Per Olof Berggren, Jang Hyun Choi, Pann Ghill Suh, Sung Ho Ryu

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Muscle atrophy occurs under various catabolic conditions, including insulin deficiency, insulin resistance, or increased levels of glucocorticoids. This results from reduced levels of insulin receptor substrate 1 (IRS-1), leading to decreased phosphatidylinositol 3-kinase activity and thereby activation of FoxO transcription factors. However, the precise mechanism of reduced IRS-1 under a catabolic condition is unknown. Here, we report that C1-Ten is a novel protein tyrosine phosphatase (PTPase) of IRS-1 that acts as a mediator to reduce IRS-1 under a catabolic condition, resulting in muscle atrophy. C1-Ten preferentially dephosphorylated Y612 of IRS-1, which accelerated IRS-1 degradation. These findings suggest a novel type of IRS-1 degradation mechanism which is dependent on C1-Ten and extends our understanding of the molecular mechanism of muscle atrophy under catabolic conditions. C1-Ten expression is increased by catabolic glucocorticoid and decreased by anabolic insulin. Reflecting these hormonal regulations, the muscle C1-Ten is upregulated in atrophy but downregulated in hypertrophy. This reveals a previously unidentified role of C1-Ten as a relevant PTPase contributing to skeletal muscle atrophy.

Original languageEnglish
Pages (from-to)1608-1620
Number of pages13
JournalMolecular and cellular biology
Volume33
Issue number8
DOIs
Publication statusPublished - 2013 Apr

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Koh, A., Lee, M. N., Yang, Y. R., Jeong, H., Ghim, J., Noh, J., Kim, J., Ryu, D., Park, S., Song, P., Koo, S. H., Leslie, N. R., Berggren, P. O., Choi, J. H., Suh, P. G., & Ryu, S. H. (2013). C1-Ten is a protein tyrosine phosphatase of insulin receptor substrate 1 (IRS-1), regulating IRS-1 stability and muscle atrophy. Molecular and cellular biology, 33(8), 1608-1620. https://doi.org/10.1128/MCB.01447-12