Integrin-linked kinase stabilizes myotendinous junctions and protects muscle from stress-induced damage

Hao Ven Wang, Ling Wei Chang, Klara Brixius, Sara A. Wickström, Eloi Montanez, Ingo Thievessen, Martin Schwander, Ulrich Müller, Wilhelm Bloch, Ulrike Mayer, Reinhard Fässler

研究成果: Article

70 引文 斯高帕斯(Scopus)

摘要

Skeletal muscle expresses high levels of integrin-linked kinase (ILK), predominantly at myotendinous junctions (MTJs) and costameres. ILK binds the cytoplasmic domain of β1 integrin and mediates phosphorylation of protein kinase B (PKB)/Akt, which in turn plays a central role during skeletal muscle regeneration. We show that mice with a skeletal muscle-restricted deletion of ILK develop a mild progressive muscular dystrophy mainly restricted to the MTJs with detachment of basement membranes and accumulation of extracellular matrix. Endurance exercise training enhances the defects at MTJs, leads to disturbed subsarcolemmal myofiber architecture, and abrogates phosphorylation of Ser473 as well as phosphorylation of Thr308 of PKB/Akt. The reduction in PKB/Akt activation is accompanied by an impaired insulin-like growth factor 1 receptor (IGF-1R) activation. Coimmunoprecipitation experiments reveal that the β1 integrin subunit is associated with the IGF-1R in muscle cells. Our data identify the β1 integrin-ILK complex as an important component of IGF-1R/insulin receptor substrate signaling to PKB/Akt during mechanical stress in skeletal muscle.

原文English
頁(從 - 到)1037-1049
頁數13
期刊Journal of Cell Biology
180
發行號5
DOIs
出版狀態Published - 2008 三月 10

All Science Journal Classification (ASJC) codes

  • Cell Biology

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    Wang, H. V., Chang, L. W., Brixius, K., Wickström, S. A., Montanez, E., Thievessen, I., Schwander, M., Müller, U., Bloch, W., Mayer, U., & Fässler, R. (2008). Integrin-linked kinase stabilizes myotendinous junctions and protects muscle from stress-induced damage. Journal of Cell Biology, 180(5), 1037-1049. https://doi.org/10.1083/jcb.200707175