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  • Original Paper
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Positive regulation of skeletal myogenesis by R-Ras

Oncogene volume 19, pages 1138–1146 (2000)Cite this article

Abstract

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.

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Acknowledgements

We are grateful to Yasuhisa Fukui, Mikako Shirouzu and Shigeyuki Yokoyama for p110 cDNA and pGEX-2T-PI3K-RBD, to David V Goeddel for R-ras cDNA, to Mariko Kobayashi and Shintaro Iwashita for pOPRSV1-R-ras GAP, and to Hironori Edamatsu and Hiroshi Itoh for pOPRSV1-H-rasG12V. We also thank Shin Mizutani, Kaoru Inouye, Motoshi Nagao, Junji Yamauchi, and all members of our laboratory for helpful discussion. This work was supported by Grants 10680666 and 11160204 (to H Koide) from the Ministry of Education, Science, Sports and Culture of Japan, and by CREST (Core Research for Evolutional Science and Technology) of Japan Science and Technology Corporation (JST). Our laboratory at Tokyo Institute of Technology is supported by funds donated by Schering-Plough Corporation.

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  1. Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, Nagatsuta, Midori-ku, Yokohama, Japan

    Jotaro Suzuki, Yoshito Kaziro & Hiroshi Koide

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Suzuki, J., Kaziro, Y. & Koide, H. Positive regulation of skeletal myogenesis by R-Ras. Oncogene 19, 1138–1146 (2000). https://doi.org/10.1038/sj.onc.1203402

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