Reference - Detail
|Author||Suzuki J, Yamazaki Y, Li G, Kaziro Y, Koide H.|
|Title||Involvement of Ras and Ral in chemotactic migration of skeletal myoblasts.|
|Journal||Mol. Cell. Biol.|
In skeletal myoblasts, Ras has been considered to be a strong inhibitor of myogenesis. Here, we demonstrate that Ras is involved also in the chemotactic response of skeletal myoblasts. Expression of a dominant-negative mutant of Ras inhibited chemotaxis of C2C12 myoblasts in response to basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and insulin-like growth factor 1 (IGF-1), key regulators of limb muscle development and skeletal muscle regeneration. A dominant-negative Ral also decreased chemotactic migration by these growth factors, while inhibitors for phosphatidylinositol 3-kinase and mitogen-activated protein kinase kinase (MEK) showed no effect. Activation of the Ras-Ral pathway by expression of an activated mutant of either Ras, the guanine-nucleotide dissociation stimulator for Ral, or Ral resulted in increased motility of myoblasts. The ability of Ral to stimulate motility was reduced by introduction of a mutation which prevents binding to Ral-binding protein 1 or phospholipase D. These results suggest that the Ras-Ral pathway is essential for the migration of myoblasts. Furthermore, we found that Ras and Ral are activated in C2C12 cells by bFGF, HGF and IGF-1 and that the Ral activation is regulated by the Ras- and the intracellular Ca(2+)-mediated pathways. Taken together, our data indicate that Ras and Ral regulate the chemotactic migration of skeletal muscle progenitors.
|MeSH||Animals Butadienes / pharmacology Calcimycin / pharmacology Calcium / metabolism Cell Line Cell Movement / drug effects Cell Movement / genetics Chemotaxis / drug effects Chemotaxis / physiology* Chromones / pharmacology Egtazic Acid / analogs & derivatives Egtazic Acid / pharmacology Enzyme Inhibitors / pharmacology Extracellular Matrix Proteins / chemistry Extracellular Matrix Proteins / metabolism Genes, ras Growth Substances / pharmacology Insulin-Like Growth Factor I / metabolism Insulin-Like Growth Factor I / pharmacology Isopropyl Thiogalactoside / pharmacology MAP Kinase Kinase Kinase 1* Mice Morpholines / pharmacology Muscle, Skeletal / cytology* Muscle, Skeletal / metabolism* Nitriles / pharmacology Phosphatidylinositol 3-Kinases / antagonists & inhibitors Phosphatidylinositol 3-Kinases / metabolism Protein-Serine-Threonine Kinases / antagonists & inhibitors Protein-Serine-Threonine Kinases / metabolism Signal Transduction ral GTP-Binding Proteins / genetics ral GTP-Binding Proteins / metabolism* ras Proteins / genetics ras Proteins / metabolism*|
|WOS Category||BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY|
|Human and Animal Cells|