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 journalArticlepeer-review

30 Citations (Scopus)


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
Issue number8
Publication statusPublished - Apr 2013


  • Animals
  • Cell Line
  • Dexamethasone
  • Down-Regulation
  • Glucocorticoids
  • HEK293 Cells
  • Humans
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Male
  • Mice
  • Mice, Obese
  • Muscle Fibers, Skeletal
  • Muscular Atrophy
  • Phosphatidylinositol 3-Kinase
  • Phosphoprotein Phosphatases
  • Phosphorylation
  • Protein Stability
  • RNA Interference
  • RNA, Small Interfering
  • Signal Transduction


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