RRC ID 39492
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.
Abstract 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.
Volume 20(13)
Pages 4658-65
Published 2000-7
DOI 10.1128/mcb.20.13.4658-4665.2000
PMID 10848592
PMC PMC85875
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*
IF 3.813
Times Cited 72
Human and Animal Cells