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

18 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 1
Externally publishedYes

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Insulin Receptor Substrate Proteins
Protein Tyrosine Phosphatases
Muscular Atrophy
Glucocorticoids
Phosphatidylinositol 3-Kinase
Insulin
Hypertrophy
Atrophy
Insulin Resistance
Skeletal Muscle
Transcription Factors
Down-Regulation
Muscles

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

C1-Ten is a protein tyrosine phosphatase of insulin receptor substrate 1 (IRS-1), regulating IRS-1 stability and muscle atrophy. / Koh, Ara; Lee, Mi Nam; Yang, Yong Ryoul; Jeong, Heeyoon; Ghim, Jaewang; Noh, Jeongeun; Kim, Jaeyoon; Ryu, Dongryeol; Park, Sehoon; Song, Parkyong; Koo, Seung-Hoi; Leslie, Nick R.; Berggren, Per Olof; Choi, Jang Hyun; Suh, Pann Ghill; Ryu, Sung Ho.

In: Molecular and Cellular Biology, Vol. 33, No. 8, 01.04.2013, p. 1608-1620.

Research output: Contribution to journalArticle

Koh, A, Lee, MN, Yang, YR, Jeong, H, Ghim, J, Noh, J, Kim, J, Ryu, D, Park, S, Song, P, Koo, S-H, Leslie, NR, Berggren, PO, Choi, JH, Suh, PG & Ryu, SH 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, vol. 33, no. 8, pp. 1608-1620. https://doi.org/10.1128/MCB.01447-12
Koh, Ara ; Lee, Mi Nam ; Yang, Yong Ryoul ; Jeong, Heeyoon ; Ghim, Jaewang ; Noh, Jeongeun ; Kim, Jaeyoon ; Ryu, Dongryeol ; Park, Sehoon ; Song, Parkyong ; Koo, Seung-Hoi ; Leslie, Nick R. ; Berggren, Per Olof ; Choi, Jang Hyun ; Suh, Pann Ghill ; Ryu, Sung Ho. / C1-Ten is a protein tyrosine phosphatase of insulin receptor substrate 1 (IRS-1), regulating IRS-1 stability and muscle atrophy. In: Molecular and Cellular Biology. 2013 ; Vol. 33, No. 8. pp. 1608-1620.
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