Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Skeletal muscle expresses high levels of integrin-linked kinase (ILK), predominantly at myotendinous junctions (MTJs) and costameres. ILK binds the cytoplasmic domain of beta1 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 beta1 integrin subunit is associated with the IGF-1R in muscle cells. Our data identify the beta1 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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PMID:Integrin-linked kinase stabilizes myotendinous junctions and protects muscle from stress-induced damage. 1833 23

Mechanical instability of skeletal muscle cells is the major cause of congenital muscular dystrophy. Here we show that the zebrafish lost-contact mutant, that lacks a functional integrin-linked kinase (ilk) gene, suffers from mechanical instability of skeletal muscle fibres. With genetic and morpholino knock-down experiments we demonstrate that: 1) laminin, itgalpha7, Ilk and beta-parvin are all critical for mechanical stability in skeletal muscles. 2) Ilk acts redundantly with the dystrophin/dystroglycan adhesion complex in maintaining mechanical stability of skeletal muscles. 3) Ilk protein is recruited to the myotendinous junctions, which requires the ECM component laminin and the presence of itgalpha7 in the sarcolemma. 4) Ilk, unexpectedly, is dispensable for formation of the adhesion complex. Ilk, however, is required for strengthening the adhesion of the muscle fibre with the ECM and this activity requires the presence of a functional kinase domain in Ilk. 5) We identified a novel interaction between Ilk and the mechanical stretch sensor protein MLP. Thus, Ilk is an essential intracellular component downstream of laminin and itgalpha7, providing strengthening of skeletal muscle fibre adhesion with the ECM and therefore qualified as a novel candidate gene for congenital muscular dystrophy.
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PMID:Zebrafish integrin-linked kinase is required in skeletal muscles for strengthening the integrin-ECM adhesion complex. 1843 6