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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Barbacid, M., 1987, ras genes, Annual. Rev. Biochem., (in press).
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.
Berridge, M.J., 1984, Inositol triphosphate and diacylglycerol as second messengers, Biochem. J., 220: 345–360.
Brugge, J.S., 1986, The p35/p36 substrates of protein-tyrosine kinases as inhibitors of phospholipase A2, Cell, 46: 149–150.
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.
Cockcroft, S. and Gomperts, B.D., 1985, Role of guanine nucleotide binding protein in the activation of polyphosphoinositide phosphodiesterase, Nature, 314: 534–536.
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.
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.
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.
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, 307:521–527
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.
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.
Furth, M.E., Aldrich, T.H. and Cordon-Cordo, C., 1987, Expression of ras proto-oncogene in normal human tissues, Oncogene, 1: 47–58.
Gilman, A.G., 1984, G-proteins and dual control of adenylate cyclase, Cell, 36: 577–579.
Hirata, F., 1981, The regulation of lipomodulin, a phospholipase inhibitory protein, in rabbit neurophils by phosphorylation, J. Biol. Chem, 256: 7730–7733.
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.
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.
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.
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.
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.
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.
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.
Ruley, H.E., 1983, Adenovirus early region lA enables viral and cellular transforming genes to transform primary cells in culture, Nature, 304: 602–606.
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.
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.
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.
Stacey, D.W., and Allfrey, V.G., 1977, Evidence for the autophagy of microinjected proteins in HeLa cells, J. Cell Biol., 75: 807–817.
Stacey, D.W., and Kung, H.-F., 1984, Transformation of NIH 3T3 cells by microinjection of Ha-ras p21 protein, Nature, 310: 508–511.
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.
Stacey, D.W., DeGudicibus, S.R.., and Smith, M.R., 1987, Cellular ras activity and tumor cell proliferation, Exptl. Cell Res., (in press).
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.
Yu, C.-L., Tsai, M.-W., and Stacey, D.W., Cellular ras activity and phospholipid metabolism, (in review).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1988 Springer Science+Business Media New York
About this chapter
Cite this chapter
Stacey, D.W. (1988). The ras Pathway: A Model for the Control of Proliferation in Animal Cells. In: Kudlow, J.E., MacLennan, D.H., Bernstein, A., Gotlieb, A.I. (eds) Biology of Growth Factors. Advances in Experimental Medicine and Biology, vol 234. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-1980-2_11
Download citation
DOI: https://doi.org/10.1007/978-1-4757-1980-2_11
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4757-1982-6
Online ISBN: 978-1-4757-1980-2
eBook Packages: Springer Book Archive