Positive regulation of skeletal myogenesis by R-Ras.
Most of the proteins in the Ras-family proteins, including Ras, Rap and TC21, have been reported to be strong inhibitors of skeletal myogenesis. Here we show that R-Ras, another member of this family, promotes terminal differentiation of C2C12 skeletal myoblasts. In contrast to Ras, which induced a markedly transformed phenotype of C2C12 cells, an activated mutant of R-Ras (R-RasQ87L) did not exhibit any inhibitory effect on the differentiation of C2C12 cells, but enhanced the formation of multinucleated myotubes. Although R-RasQ87L showed little effect on induction of two muscle-specific proteins, creatine kinase and myogenin, it prevented cell death during myoblast differentiation, probably through Akt activation and Bcl-xL induction. Motility of C2C12 cells, which may be involved in fusion of myoblasts, was also stimulated by R-RasQ87L. Furthermore, we observed a transient activation of endogenous R-Ras during differentiation of C2C12 cells. The ectopic expression of R-Ras GAP inhibited the differentiation. These results suggest that R-Ras has a positive effect on the terminal differentiation of myoblasts and may be involved in the program of skeletal myogenesis.
Suzuki
J
J
Faculty of Bioscience, Tokyo Institute of Technology, Nagatsuta, Midori-ku, Yokohama, Japan.
Kaziro
Y
Y
Koide
H
H
D000818:Animals; D016923:Cell Death; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement; D003402:Creatine Kinase / Q000096:biosynthesis; D004790:Enzyme Induction; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D009154:Mutation; D018008:Myogenin / Q000096:biosynthesis; D015513:Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D018631:ras Proteins / Q000235:genetics / Q000502:physiology*
C503801:Myog protein, mouse; D018008:Myogenin; D015513:Oncogene Proteins; D003402:Creatine Kinase; D020558:GTP Phosphohydrolases; C513254:Rras protein, mouse; D018631:ras Proteins