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

Research output: Contribution to journalArticlepeer-review

84 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1037-1049
Number of pages13
JournalJournal of Cell Biology
Issue number5
Publication statusPublished - 2008 Mar 10

All Science Journal Classification (ASJC) codes

  • Cell Biology


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