Titre :
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Studying MAP kinase phosphorylation in Duchenne muscular dystrophy by proteomic approaches (abstract : congrès international de Myologie, 2005)
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contenu dans :
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Auteurs :
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Congrès international de myologie 2005 (International Congress of Myology 2005; 9-13 mai 2005; Nantes, France) ;
Guével A ;
Feron M ;
Arnaud MC ;
McIlroy WE ;
Sakanyan V
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Type de document :
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Article
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Année de publication :
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2005
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Pages :
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p. 92
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Langues:
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Anglais
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Mots-clés :
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bêta-dystroglycane
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colloque
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dégenérescence de la fibre musculaire
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dystrophie musculaire de Duchenne
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MAP kinase
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muscle squelettique
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phosphorylation
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protéine
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souris mdx
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Résumé :
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Communication n° 385. Dystrophin deficiency leads to disassembly of the dystrophin-glycoprotein complex (DGC) that determines pathophysiological changes in Duchenne muscular dystrophy (DMD) patients. Beta-dystroglycan, part of the DGC, interacts with focal adhesion kinase (FAK) involved in the Ras/mitogen-activated protein kinase (MAPK) signaling pathway. Our antibody array-based data indicate that the phosphorylation level of FAK, Pyk2 and Raf kinases appears to be lower in biopsies of DMD patients compared with non-dystrophic controls. This observation led us to hypothesise that downstream proteins of the ERK MAP kinase pathway might be involved in the development of muscular dystrophies. The aim of the current work is to evaluate the role and contribution of kinase signalling pathways to muscle degeneration in muscular dystrophy using conventional methods and high-throughput protein array technology. Here, we use total protein arrays in order to assess directly target proteins in numerous samples in a single assay. We have extracted total protein from cells or tissues (tibialis anterior and diaphragm) of wild-type and mdx mice and printed the analytes on a nitrocellulose membrane. The assessment of protein phosphorylation profile was performed using selected monoclonal antibodies against phosphorylated and total target proteins followed by the detection of fluorescent signals with near-infrared labeled secondary antibodies. We compared target protein behavior under various experimental conditions. In particular, the impact of activation of satellite cells with PDGF or inhibition of ERK activity with UO126 was monitored by following protein expression and phosphorylation. Encouraging preliminary data suggest that the ERK MAP kinases are differentially activated in skeletal muscles of mdx mice. This proteomic study will help to identify proteins as potential biomarkers associated with defective phosphorylation in muscular dystrophy.
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