1. Skeletal Muscle Signaling Pathway through the Dystrophin Glycoprotein Complex and Rac1
- Author
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Yan Wen Zhou, Harry W. Jarrett, and Shilpa A. Oak
- Subjects
rac1 GTP-Binding Protein ,Macromolecular Substances ,Myoblasts, Skeletal ,Recombinant Fusion Proteins ,Muscle Proteins ,In Vitro Techniques ,Protein Serine-Threonine Kinases ,Models, Biological ,Biochemistry ,Cell Line ,Dystrophin ,Mice ,Laminin ,medicine ,Animals ,Myocyte ,Muscle, Skeletal ,Laminin binding ,Molecular Biology ,Adaptor Proteins, Signal Transducing ,GRB2 Adaptor Protein ,Glycoproteins ,Syntrophin ,biology ,JNK Mitogen-Activated Protein Kinases ,Membrane Proteins ,Proteins ,Skeletal muscle ,Cell Biology ,musculoskeletal system ,Molecular biology ,Enzyme Activation ,medicine.anatomical_structure ,p21-Activated Kinases ,Dystrophin-Associated Proteins ,biology.protein ,Phosphorylation ,Rabbits ,Mitogen-Activated Protein Kinases ,Signal transduction ,C2C12 ,Signal Transduction - Abstract
The dystrophin glycoprotein complex has been proposed to be involved in signal transduction. Here we have shown that laminin binding causes syntrophin to recruit Rac1 from the rabbit skeletal muscle. Laminin-Sepharose and syntrophin-Sepharose bind a protein complex containing Rac1 from the muscle membranes. The presence of heparin, which inhibits laminin interactions, prevents recruitment of Rac1. The dystrophin glycoprotein complex recruits Rac1 via syntrophin through a Grb2.Sos1 complex. A syntrophin antibody also prevents recruitment of Rac1, suggesting that the signaling complex requires syntrophin. PAK1 is in turn bound by Rac1. c-Jun NH2-terminal kinase-p46 is phosphorylated and activated only when laminin is present, and the p54 isoform is activated when laminin is depleted or binding is inhibited with heparin. In the presence of laminin, c-Jun is activated in both skeletal muscle microsomes and in C2C12 myoblasts, and proliferation increases in C2C12 myoblasts. We postulate that this pathway signals muscle homeostasis and hypertrophy.
- Published
- 2003