title: C1-Ten is a protein tyrosine phosphatase of insulin receptor substrate 1 (IRS-1), regulating IRS-1 stability and muscle atrophy.
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.
authors: Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, South Korea.
authors: Ara
authors: A
authors: Koh
authors: Mi Nam
authors: MN
authors: Lee
authors: Yong Ryoul
authors: YR
authors: Yang
authors: Heeyoon
authors: H
authors: Jeong
authors: Jaewang
authors: J
authors: Ghim
authors: Jeongeun
authors: J
authors: Noh
authors: Jaeyoon
authors: J
authors: Kim
authors: Dongryeol
authors: D
authors: Ryu
authors: Sehoon
authors: S
authors: Park
authors: Parkyong
authors: P
authors: Song
authors: Seung-Hoi
authors: SH
authors: Koo
authors: Nick R
authors: NR
authors: Leslie
authors: Per-Olof
authors: PO
authors: Berggren
authors: Jang Hyun
authors: JH
authors: Choi
authors: Pann-Ghill
authors: PG
authors: Suh
authors: Sung Ho
authors: SH
authors: Ryu
mesh_terms: D000818:Animals; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation; D005938:Glucocorticoids / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008820:Mice, Obese; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D055550:Protein Stability; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction; D000070876:Tensins
chemical_list: D005938:Glucocorticoids; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D034741:RNA, Small Interfering; D000070876:Tensins; D003907:Dexamethasone; D058539:Phosphatidylinositol 3-Kinase; D010749:Phosphoprotein Phosphatases; C511707:Tns2 protein, mouse
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