The ras Pathway: A Model for the Control of Proliferation in Animal Cells

  • Dennis W. Stacey
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 234)

Abstract

Scrupulous control over cellular proliferation is essential for the survival of a multicellular organism, yet little is known about the mechanism of this control. A variety of factors are known to influence cell division in both positive and negative ways. These include diffusible factors and the results of cell-cell contact. While the ultimate decision concerning cell division is most likely made at the molecular level within a specific cell, this decision must be based upon the signals received from outside the cell. In this study data and hypotheses are presented primarily regarding the means by which extracellular proliferative signals are transferred into the cell. This discussion, therefore, represents an important but limited aspect of the control of proliferation within the organism. While the discussion will center primarily upon a presentation of data, hypotheses relating to these data will also be included. In many cases, the hypotheses are only speculative at present.

Keywords

Phosphatidic Acid Thymidine Incorporation Mitogenic Stimulation Thymidine Labelling Cellular Oncogene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Barbacid, M., 1987, ras genes, Annual. Rev. Biochem., (in press).Google Scholar
  2. Bar-Sagi, D. and Feramisco, J.R., 1986, Induction of membrane ruffling and fluid-phase pinocytosis in quiescent fibroblasts by ras proteins. Science, 233: 1061–1068.CrossRefPubMedGoogle Scholar
  3. Berridge, M.J., 1984, Inositol triphosphate and diacylglycerol as second messengers, Biochem. J., 220: 345–360.PubMedGoogle Scholar
  4. Brugge, J.S., 1986, The p35/p36 substrates of protein-tyrosine kinases as inhibitors of phospholipase A2, Cell, 46: 149–150.CrossRefPubMedGoogle Scholar
  5. Chambard, J.C., Paris, S., L’Allemain, G., and Pouyssegur, J., 1987, Two growth factor signalling pathways in fibroblasts distinguished by pertusis toxin, Nature, 326: 800–803.CrossRefPubMedGoogle Scholar
  6. Cockcroft, S. and Gomperts, B.D., 1985, Role of guanine nucleotide binding protein in the activation of polyphosphoinositide phosphodiesterase, Nature, 314: 534–536.CrossRefPubMedGoogle Scholar
  7. Davidson, F.F., Dennis, E.A., Powell, M., and Glenney, J.R., 1987, Inhibition of phospholipase A9 by “lipocortins” and calpactins,an effect of binding to substrate phospholipids, J.Biol. Chem., 262: 1698–1705.PubMedGoogle Scholar
  8. Deshpande, A.K., and Kung, H.-F., 1987, Insulin induction of Xenopus Bevis oocyte maturation is inhibited by monoclonal antibody against p2lras proteins, Mol. Cell. Biol., 3: 1285–1288.Google Scholar
  9. Doolittle, R.F., Hunkapiller, M.W., Hood, L.E., Devare, S.G., Robbins, K.C., Aaronson, S.A. and Antoniades, H.N., 1983, Simian sarcoma virus one gene, v-s?s, is derived from the gene (or genes) encoding a platelet-derived growth factor, Science, 221: 275–277.CrossRefPubMedGoogle Scholar
  10. Downward, J., Yarden, Y. Mayes, E. Scrace, G. Totty, N., Stockwell, P., Ullrich, A., Schlessinger, J. and Waterfield, M.D., 1984, Close similarity of epidermal growth factor receptor and v-erb B oncogene protein sequences, Nature, 307:521–527CrossRefPubMedGoogle Scholar
  11. Farese, R.V., Konda, T.S., Davis, J.S., Standaert, M.L., Pollet, R.J., and Cooper, D.R., 1987, Insulin rapidly increases diacylglycerol by activating de novo phosphatidic acid synthesis, Science, 236: 586–589.CrossRefPubMedGoogle Scholar
  12. Furth, M.E., Davis, L.J., Fleurdelys, B. and Scolnick, E.M., 1982, Monoclonal antibodies to the p21 products of the transforming gene of Harvey murine sarcoma virus and the cellular ras gene family, J. Virol., 43: 294–304.PubMedGoogle Scholar
  13. Furth, M.E., Aldrich, T.H. and Cordon-Cordo, C., 1987, Expression of ras proto-oncogene in normal human tissues, Oncogene, 1: 47–58.PubMedGoogle Scholar
  14. Gilman, A.G., 1984, G-proteins and dual control of adenylate cyclase, Cell, 36: 577–579.CrossRefPubMedGoogle Scholar
  15. Hirata, F., 1981, The regulation of lipomodulin, a phospholipase inhibitory protein, in rabbit neurophils by phosphorylation, J. Biol. Chem, 256: 7730–7733.PubMedGoogle Scholar
  16. Kung, H.F., Smith, M.R., Bekesi, E., Manne, V. and Stacey, D.W., 1986, Reversal of transformed phenotype by monoclonal antibodies against Ha-ras p21 proteins, Exp. Cell Res., 162: 363–371.CrossRefPubMedGoogle Scholar
  17. Lacal, J.G., Santos, E., Notario, V., Barbacid, M., Yamazaki, S., Kung, H.-F., Seamans, C., McAndrew, S., and Crowl,R., 1984, Expression of normal and transforming H-ras genes in Escherichla Coil and purification of their encoded p21 proteins, Proc. Natl. Acad. Scia USA, 81: 5305–5309.CrossRefGoogle Scholar
  18. Mercer, W.E., Avignolo, C., and Baserga, R., 1984, Role of the p53 protein in cell proliferation as studied by microinjection of monoclonal antibodies, Mol. Cell. Biol., 4: 276–281.PubMedGoogle Scholar
  19. Moolénaar, W.H., Kruijer, W. Tilly, B.C., Verlaan, I. Bierman, A.J. and deLaat, S.W. (1986). Growth factor-like action of phosphatidic acid. Nature 323: 171–173.CrossRefPubMedGoogle Scholar
  20. Mulcahy, L.S., Smith, M.R. and Stacey, D.W., 1985, Requirement for ras proto-oncogene function during serum-stimulated growth of NIH3T3 cells, Nature, 313: 241–243.CrossRefPubMedGoogle Scholar
  21. Muller, R., Bravo, R, Burckhardt, J., and Curran, T., 1984, Induction of c-fos gene and protein by growth factors precedes activation of c-myc, Nature, 312: 716–720.CrossRefPubMedGoogle Scholar
  22. Papageorge, A.G., Willumsen, B.M., Johnsen, M., Kung, H.-F., Stacey, D.W., Vass, W.C. and Lowy, D.R., 1986, A transforming ras gene can provide an essential function ordinarily supplied by an endogenous ras gene, Mol. Cell.Biol., 6: 1843–1846.PubMedGoogle Scholar
  23. Ruley, H.E., 1983, Adenovirus early region lA enables viral and cellular transforming genes to transform primary cells in culture, Nature, 304: 602–606.CrossRefPubMedGoogle Scholar
  24. Scolnick, E.M., Papageorge,’ A.G. and Shih, T.Y., 1979, Guanine nucleotide binding activity as an assay for arc protein of rat-derived murine sarcoma viruses,Proc. Natl. Acad. Sci. USA, 76: 5355–5359.CrossRefGoogle Scholar
  25. Sherr, C.J., Rettenmier, C.W., Sacca, R., Roussel, M.F., Look, A.T. and Stanley, E.R., 1985, The c-fias proto-onçogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1, Cell, 41: 665–676.CrossRefPubMedGoogle Scholar
  26. Smith, M.R., DeGudicibus, S.J. and Stacey, D.W., 1986, Requirement for c-z-as proteins during viral oncogene transformation, Nature, 320: 540–543.CrossRefPubMedGoogle Scholar
  27. Stacey, D.W., and Allfrey, V.G., 1977, Evidence for the autophagy of microinjected proteins in HeLa cells, J. Cell Biol., 75: 807–817.CrossRefPubMedGoogle Scholar
  28. Stacey, D.W., and Kung, H.-F., 1984, Transformation of NIH 3T3 cells by microinjection of Ha-ras p21 protein, Nature, 310: 508–511.CrossRefPubMedGoogle Scholar
  29. Stacey, D.W., Watson, T., Kung, H.-F., and Curran, T., 1987, Microinjection of transforming ras protein induces c-fos expression, Mol. Cell. Biol., 7: 523–527.PubMedGoogle Scholar
  30. Stacey, D.W., DeGudicibus, S.R.., and Smith, M.R., 1987, Cellular ras activity and tumor cell proliferation, Exptl. Cell Res., (in press).Google Scholar
  31. Sweet, R.W., Yokoyama, S., Kamata, T., Feramisco, J.R., Rosenberg, M. and Gross, M. (1984). The product of ras is a GTPase and the T24 oncogenic mutant is deficient in this activity. Nature 311: 273–275.CrossRefPubMedGoogle Scholar
  32. Yu, C.-L., Tsai, M.-W., and Stacey, D.W., Cellular ras activity and phospholipid metabolism, (in review).Google Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Dennis W. Stacey
    • 1
  1. 1.The Roche Institute of Molecular BiologyRoche Research CenterNutleyUSA

Personalised recommendations