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The ras Oncogene and Myogenic Commitment and Differentiation

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ras Oncogenes

Abstract

When proliferating BC3H1 muscle cells are shifted to low serum conditions, they exit from the cell cycle and differentiate, activating a family of muscle-specific genes. Addition of the purified growth factors, fibroblast growth factor (FGF) or thrombin reverses this process and stimulates these cells to reenter the cell cycle. Pertussis toxin (PT) blocks thrombin’s, but not FGF’s, effects on muscle proliferation/differentiation. Thrombin, therefore, requires a G protein to transduce its signal. In addition, PT promoted differentiation in the presence of high concentrations of serum. Serum then contains a mitogen that signals through a PT-sensitive pathway in order to promote proliferation and inhibit muscle gene transcription. Transfection of the activated Ha-ras oncogene into BC3H1 and 10T1/2 cells blocked muscle differentiation in both of these lines. PT could not rescue the ras-mediated inhibition of differentiation. These results suggest that G protein-like molecules play important roles in transducing growth factor signals that control myogenesis.

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References

  • Davis, R.L., Weintraub, H., and Lassar, A. B., 1987, Expression of a single transfected cDNA converts fibroblasts to myoblasts, Cell, 51:987.

    Article  PubMed  CAS  Google Scholar 

  • Florini, J.R. and Magri, K.A.,1988, Effects of growth factors on myogenic differentiation, Amer. J. Physiol. (in press).

    Google Scholar 

  • Gilman, A.G.,1987, G proteins: tranducers of receptor-generated signals, Ann. Rev. Biochem., 56:615.

    Article  PubMed  CAS  Google Scholar 

  • Hurley, J.B., Simon, M.I., Teplow, D.B., Robishaw, J.D., Gilman, A.G., 1984, Homologies between signal transducing G proteins and ras gene products, Science, 226:860.

    Article  PubMed  CAS  Google Scholar 

  • Kelvin, D.J., Simard, G., Tai, H.H., Yamaguchi, T.P., and Connolly, J.A., 1989a, Growth factors, signalling pathways and the regulation of proliferation and differentiation in BC3H1 muscle cells. I. A pertussis toxin sensitive pathway is involved, J. Cell Biol., 108:159.

    Article  PubMed  CAS  Google Scholar 

  • Kelvin, D.J., Simard, G., Sue-A-Quan, A., and Connolly, J.A., 1989b, Growth factors, signalling pathways and the regulation of proliferation and differentiation in BC3H1 muscle cells. II. Two signalling pathways distinguished by pertussis toxin and a potential role for the ras oncogene, J. Cell Biol., 108:169.

    Article  PubMed  CAS  Google Scholar 

  • Kelvin, D.J., Simard, G., and Connolly, J.A., 1989c, FGF and EGF act synergistically to induce proliferation in BC3H1 myblasts, J. Cell. Physiol. (in press).

    Google Scholar 

  • Kimelman, D. and Kirschner, M., 1987, Synergistic induction of mesoderm by FGF and TGF-B and the identification of an mRNA coding for FGF in the early X Xenopus embryo, Cell, 51:869.

    Article  PubMed  CAS  Google Scholar 

  • Lathrop, B., Olson, E., and Glaser, L,1985, Control by fibroblast growth factor of differentiation in the BC3H1 muscle cell line, J. Cell Biol., 100:1540.

    Article  Google Scholar 

  • Mercola, M., and Stiles, C.D., 1988, Growth factor superfamilies and mammalian embryogenesis, Development, 102:451.

    PubMed  CAS  Google Scholar 

  • Merlie, J. P., Buckingham, M.E., and Whalen, R.G., 1977, Molecular aspects of myogenesis, Curr. Top. Dev. Biol., 11:61.

    Article  PubMed  CAS  Google Scholar 

  • Munson, R., Caldwell, K.L., and Glaser, L., 1982, Multiple controls for the synthesis of muscle-specific proteins in BC3H1 cells, J. Cell Biol., 92:350.

    Article  PubMed  CAS  Google Scholar 

  • Olson, E.N., Sternberg, E., Hu, J.S., Spizz, G., and Wilcox, C., 1986, Regulation of myogenic differentiation by type-B transforming growth factor. J. Cell Biol., 103:1799.

    Article  PubMed  CAS  Google Scholar 

  • Olson, E.N., Spizz, G., and Tainsky, M.A.,1987, The oncogenic form of N-ras or H-ras prevent skeletal myblast differentiation, Mol. Cell. Biol.,7:2104–2111.

    PubMed  CAS  Google Scholar 

  • Payne, P.A., Olson, E.N., Hsiau, P., Roberts, M.B., Perryman, M.B., and Schneider, M.D., 1987, An activated c-Ha-ras allele block the induction of musclespecific genes whose expression is contingent upon mitogen withdrawal, Proc. Natl. Acad. Sci. U.S.A., 84:8956.

    Article  PubMed  CAS  Google Scholar 

  • Rosa, F., Roberts, A.B., Danielpour, D., Dart, L.L., Sporn, M.B., and Dawid, I.B., 1988, Mesoderm induction in amphibians: the role of TGF-B2-like factors, Science, 239:783.

    Article  PubMed  CAS  Google Scholar 

  • Schubert, D., Harris, A.J., Devine, and C.E., Heinemann, S., 1974, Characterization of a unique muscle cell line, J. Cell Biol., 61:398.

    Article  Google Scholar 

  • Seed, J., and Hauschka, S.D.,1988, Clonal analysis of vertebrate myogenesis. VIII. Fibroblast growth factor (FGF)-dependent and FGF-independent muscle colony types during chick wing development, Dev. Biol., 128:40.

    Article  PubMed  CAS  Google Scholar 

  • Slack, J.M.W., Darlington, B.G., Heatth, J.K., and Godsave, S.F., 1987, Mesoderm induction in early Xenopus embryos by heparin-binding growth factors, Nature, 326:197.

    Article  PubMed  CAS  Google Scholar 

  • Smith, M.R., DeGudicibus, S.J., and Stacey, D.J.,1986, Requirement for c-ras proteins during viral oncogene transformation, Nature, 320:540.

    Article  PubMed  CAS  Google Scholar 

  • Tai, H.H., Shin, M.J., Simard, G., Strauch, A.R., Connolly, J.A., 1989, Signalling pathways in the inhibition of myogenic differentiation by the ras oncogene, J. Cell Biol., 107: abstr. 2738.

    Google Scholar 

  • Tapscott, S.J., Davis, R.L., Thayer, M.J., Cheng, P.-F., Weintraub, H., and Lassar, A.B., 1988, MyoD 1: A nuclear phosphoprotein requiring a myc homology region to convert fibroblasts to myoblasts, Science, 242:405.

    Article  PubMed  CAS  Google Scholar 

  • Taylor, C.W., and Merritt, J.E.,1986, Receptor coupling to polyphosphoinositide turnover: a parallel with the adenylate cyclase system, Trends Pharmacol. Sci., 7:238.

    Article  CAS  Google Scholar 

  • Taylor, S.M., and Jones, P.A., 1979, Multiple new phenotypes induced in 10T1/2 and 3T3 cells treated with 5-azacytidine, Cell, 17:771.

    Article  PubMed  CAS  Google Scholar 

  • Trimble, W.S., Johnson, P.W., Hozumi, N., and Roder, J.C., 1986, Inducible cellular transformation by a metallothionein-ras hybrid oncogene leads to natural killer cell susceptibility, Nature, 321:782.

    Article  PubMed  CAS  Google Scholar 

  • Wang, Y.-C. and Rubenstein, P.A.,1988, Epidermal growth factor controls smooth muscle a-isoactin expression in BC3H1 cells, J. Cell Biol., 106:797.

    Article  PubMed  CAS  Google Scholar 

  • Yamaguchi, T.P., Sue-A-Quan, G.T. and Connolly, J.A.,1989, An activated c-Ha-ras allele inhibits the formation of muscle colonies from 10T1/2 cells, J. Cell Biol., 107:abstr.2739.

    Google Scholar 

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© 1989 Springer Science+Business Media New York

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Yamaguchi, T.P. et al. (1989). The ras Oncogene and Myogenic Commitment and Differentiation. In: Spandidos, D. (eds) ras Oncogenes. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-1235-3_25

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  • DOI: https://doi.org/10.1007/978-1-4757-1235-3_25

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-1237-7

  • Online ISBN: 978-1-4757-1235-3

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