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

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...

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Autores principales: Wang, Hao-Ven, Chang, Ling-Wei, Brixius, Klara, Wickström, Sara A., Montanez, Eloi, Thievessen, Ingo, Schwander, Martin, Müller, Ulrich, Bloch, Wilhelm, Mayer, Ulrike, Fässler, Reinhard
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2265410/
https://www.ncbi.nlm.nih.gov/pubmed/18332223
http://dx.doi.org/10.1083/jcb.200707175
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author Wang, Hao-Ven
Chang, Ling-Wei
Brixius, Klara
Wickström, Sara A.
Montanez, Eloi
Thievessen, Ingo
Schwander, Martin
Müller, Ulrich
Bloch, Wilhelm
Mayer, Ulrike
Fässler, Reinhard
author_facet Wang, Hao-Ven
Chang, Ling-Wei
Brixius, Klara
Wickström, Sara A.
Montanez, Eloi
Thievessen, Ingo
Schwander, Martin
Müller, Ulrich
Bloch, Wilhelm
Mayer, Ulrike
Fässler, Reinhard
author_sort Wang, Hao-Ven
collection PubMed
description 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.
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spelling pubmed-22654102008-09-10 Integrin-linked kinase stabilizes myotendinous junctions and protects muscle from stress-induced damage Wang, Hao-Ven Chang, Ling-Wei Brixius, Klara Wickström, Sara A. Montanez, Eloi Thievessen, Ingo Schwander, Martin Müller, Ulrich Bloch, Wilhelm Mayer, Ulrike Fässler, Reinhard J Cell Biol Research Articles 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. The Rockefeller University Press 2008-03-10 /pmc/articles/PMC2265410/ /pubmed/18332223 http://dx.doi.org/10.1083/jcb.200707175 Text en Copyright © 2008, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Wang, Hao-Ven
Chang, Ling-Wei
Brixius, Klara
Wickström, Sara A.
Montanez, Eloi
Thievessen, Ingo
Schwander, Martin
Müller, Ulrich
Bloch, Wilhelm
Mayer, Ulrike
Fässler, Reinhard
Integrin-linked kinase stabilizes myotendinous junctions and protects muscle from stress-induced damage
title Integrin-linked kinase stabilizes myotendinous junctions and protects muscle from stress-induced damage
title_full Integrin-linked kinase stabilizes myotendinous junctions and protects muscle from stress-induced damage
title_fullStr Integrin-linked kinase stabilizes myotendinous junctions and protects muscle from stress-induced damage
title_full_unstemmed Integrin-linked kinase stabilizes myotendinous junctions and protects muscle from stress-induced damage
title_short Integrin-linked kinase stabilizes myotendinous junctions and protects muscle from stress-induced damage
title_sort integrin-linked kinase stabilizes myotendinous junctions and protects muscle from stress-induced damage
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2265410/
https://www.ncbi.nlm.nih.gov/pubmed/18332223
http://dx.doi.org/10.1083/jcb.200707175
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