Abstract
Many receptors, in response to ligand activation, trigger inositol phospholipid breakdown, which leads to rapid intracellular responses1–4. The sustained activation of this pathway is believed to be at least one of the factors involved in the stimulation of cell growth and there has been much speculation4–6 that certain oncogenes use this pathway to effect uncontrolled cellular proliferation. It has been suggested7, by analogy with the receptor-mediated control of adenylate cyclase8, that the receptor stimulation of inositol phospholipid metabolism is mediated through a guanine nucleotide regulatory protein (G-protein) called Gp (or Np). Although such a species has not been identified, there is now strong experimental evidence that this process is mediated by a G-protein distinct from the stimulatory and inhibitory G-proteins (Gs and Gi, respectively)9–12. The ras genes code for a plasma membrane protein, p21, whose only known biochemical property is a high-affinity GTPase activity13. We show here that the expression of normal p21N–ras in NIH 3T3 fibroblasts leads to the coupling of certain growth factor receptors to stimulated inositol phosphate production. We propose that the N-ras proto-oncogene encodes a protein which couples the receptors for certain growth factors to the stimulation of phospholipase C. Thus, N-ras p 21 may be the putative Gp or a functionally related protein.
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References
Michell, R. H. Biochim. biophys. Acta 415, 81–147 (1975).
Berridge, M. J. Biochem. J. 220, 345–360 (1984).
Berridge, M. J. & Irvine, R. F. Nature 312, 315–321 (1984).
Downes, C. P. & Michell, R. H. Molec. Aspects cell. Regul. 4, 2–56 (1985).
Berridge, M. J. Biotechnology 2, 541–546 (1984).
Michell, R. H. Nature 308, 770 (1984).
Gomperts, B. D. Nature 306, 64–66 (1983).
Houslay, M. D. Trends biochem. Sci. 9, 39–40 (1984).
Haslam, R. J. & Davidson, M. M. L. FEBS Lett. 174, 90–95 (1984).
Litosch, I., Wallis, C. & Fain, J. N. J. biol. Chem. 260, 5464–5471 (1985).
Gonzales, R. A. & Crews, F. T. Biochem. J. 232, 799–804 (1985).
Houslay, M. D., Bojanic, D. & Wilson, A. Biochem. J. 234, 737–740 (1986).
McGrath, J. P., Capon, D. J., Goeddel, D. V. & Levinson, A. D. Nature 310, 644–649 (1984).
Shih, C., Paddy, L. C., Murray, M. & Weinberger, R. A. Nature 290, 261–264 (1981).
Krontiris, T. G. & Cooper, G. M. Proc. natn. Acad. Sci. U.S.A. 78, 1181–1184 (1981).
Marshall, C. J., Hall, A. & Weiss, R. A. Nature 299, 171–173 (1982).
Santos, E., Tronick, S. R., Aaronson, S. A., Pulciani, S. & Barbacid, M. Nature 298,343–347 (1982).
Pulciani, S. et al. Nature 300, 539–542 (1982).
Hall, A., Marshall, C. J., Spurr, N. & Weiss, R. A. Nature 303, 396–400 (1983).
Willingham, M. C., Banks-Schlegal, S. P. & Pastan, I. E. Expl Cell Res. 149, 141–149 (1983).
Tanabe, T. et al. Nature 315, 242–245 (1985).
Zachary, I. & Rozengurt, E. Proc. natn. Acad. Sci. U.S.A. 82, 7616–7620 (1985).
Berridge, M. J., Heslop, J. P., Irvine, R. F. & Brown, K. D. Biochem. J. 222, 195–201 (1984).
Hasegawa-Sasaki, H. Biochem. J. 232, 99–109 (1985).
Heldin, C. H. & Westermark, B. Cell 37, 9–20 (1984).
Fleischman, L. F., Chahwala, S. B. & Cantley, L. Science 231, 407–410 (1986).
Kamata, T. & Feramisco, J. R. Nature 310, 147–150 (1984).
Adams, R. L. P. Expl Cell Res. 56, 49–54 (1969).
Berridge, M. J., Downes, C. P. & Hanley, M. R. Biochem. J. 206, 587–595 (1982).
Berridge, M. J., Dawson, R. M. C., Downes, C. P., Heslop, J. P. & Irvine, R. F. Biochem. J. 212, 473–482 (1983).
Furth, M. E., Davis, L. J., Fleurdelys, B. & Scolnick, E. M. J. Virol. 43, 294–304 (1982).
Moody, T. W., Carney, D. N., Cutitta, F., Quattrocchi, K. & Minna, J. D. Life Sci. 37, 105–113 (1985).
Jensen, R. T., Moody, T., Pert, C., Rivier, J. E. & Gardner, J. D. Proc. natn. Acad. Sci. U.S.A. 75, 6139–6143 (1978).
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Wakelam, M., Davies, S., Houslay, M. et al. Normal p21N-ras couples bombesin and other growth factor receptors to inositol phosphate production. Nature 323, 173–176 (1986). https://doi.org/10.1038/323173a0
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DOI: https://doi.org/10.1038/323173a0
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