C1-Ten Is a Protein Tyrosine Phosphatase of Insulin Receptor Substrate 1 (IRS-1), Regulating IRS-1 Stability and Muscle Atrophy
SCIE
SCOPUS
- Title
- C1-Ten Is a Protein Tyrosine Phosphatase of Insulin Receptor Substrate 1 (IRS-1), Regulating IRS-1 Stability and Muscle Atrophy
- Authors
- Koh, A; Lee, MN; Yang, YR; Jeong, H; Ghim, J; Noh, J; Kim, J; Ryu, D; Park, S; Song, P; Koo, SH; Leslie, NR; Berggren, PO; Choi, JH; Suh, PG; Ryu, SH
- Date Issued
- 2013-04
- Publisher
- MOLECULAR AND CELLULAR BIOLOGY
- 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.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/11703
- DOI
- 10.1128/MCB.01447-12
- ISSN
- 0270-7306
- Article Type
- Article
- Citation
- MOLECULAR AND CELLULAR BIOLOGY, vol. 33, no. 8, page. 1608 - 1620, 2013-04
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