Phosphoinositide metabolism and control of cell proliferation

  • Colin W. Taylor
Part of the NATO ASI Series book series (NSSE, volume 156)

Abstract

In most cells initiation of DNA synthesis is inexorably followed by a premitotic phase and then by mitosis, the essential control of cell proliferation is therefore the signal that commits a cell to DNA synthesis. Since cells may be stimulated to divide from various degrees of preparedness these signals differ in their complexity. Nevertheless two general problems emerge that we must address in seeking to understand how mitogens stimulate cells to proliferate. Firstly, DNA synthesis occurs in the nucleus yet mitogens are recognised by their receptors in the plasma membrane: how do occupied receptors communicate, across the cytoplasm, with the nucleus? Secondly, while mitogens are immediately recognised by their receptors, DNA synthesis typically begins many hours later: what happens during this long interval? By the usual criteria of necessity and sufficiency, it is clear that the messengers that link early events at the plasma membrane with the later initiation of DNA synthesis have not been identified. Indeed it is very likely that there are many pathways from cell-surface receptors to the nucleus and these pathways overlap and interact so that no single intracellular messenger is likely to be both necessary and sufficient to commit a cell to DNA synthesis.

Keywords

Tyrosine Kinase Activity Pertussis Toxin Inositol Phosphate Intracellular Messenger Effector Enzyme 
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.

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References

  1. Bar-Sagi, D and Feramisco, J R (1986) Science 233, 1061–1068PubMedCrossRefGoogle Scholar
  2. Berridge, M J and Irvine, R F (1984) Nature 312, 315–321PubMedCrossRefGoogle Scholar
  3. Berridge, M J, Brown, K D, Irvine, R F and Heslop, J P (1985) J. Cell Sci. Suppl 3, 187–198Google Scholar
  4. Brass, L F and Joseph S K (1985) J. Biol. Chem. 260, 15172–15179PubMedGoogle Scholar
  5. Chambard, J C, Paris, S., L’Allemain, G and Pouyssegur, J (1987) Nature 326, 800–803PubMedCrossRefGoogle Scholar
  6. Clapper, D L and Lee, H C (1985) J. Biol. Chem. 260, 13947–13954PubMedGoogle Scholar
  7. Fleischman, L F, Chahwala, S B and Cantley, L (1986) Science 231, 407–410PubMedCrossRefGoogle Scholar
  8. Hesketh, T R, Moore, J P, Morris J D H, Taylor, M V, Rogers, J., Smith, G A and Metcalfe, J C (1985) Nature 313, 481–484PubMedCrossRefGoogle Scholar
  9. Heslop, J P, Blakeley, D M, Brown, K D, Irvine, R F and Berridge, M J (1986) Cell 47, 703–709PubMedCrossRefGoogle Scholar
  10. Irvine, R F and Moor, R M (1986) Biochem. J. 240, 917–920PubMedGoogle Scholar
  11. Letterio, J., Coughlin, S and Williams, L (1986) Science 234, 1117–1119PubMedCrossRefGoogle Scholar
  12. Lopez-Rivas, A., Mendoza, S A, Nanberg, E., Sinnett-Smith, J W and Rozengurt, E (1987) Proc. Natl. Acad. Sci. 84, 5768–5772PubMedCrossRefGoogle Scholar
  13. Macara, I G, Marinetti, G V and Baldozzi, P C (1984) Proc. Natl. Acad. Sci. 81, 2778–2732CrossRefGoogle Scholar
  14. Macdonald, M L, Kuenzel, E A, Glomset, J A and Krebs, E G (1985) Proc. Natl. Acad. Sci. 82, 3993–3997PubMedCrossRefGoogle Scholar
  15. Micheli, R H (1982) Cell Calcium 3, 429–440CrossRefGoogle Scholar
  16. Moolenaar, W H, Tertoolen, L G J and de Laat, S W (1984) Nature 312, 371–374PubMedCrossRefGoogle Scholar
  17. Moolenaar, W H, Kruiger, W., Tilly, B C, Verlaan, I., Bierman, A J and de Laat S W (1986) Nature 323, 171–173PubMedCrossRefGoogle Scholar
  18. Mulcahy, L S, Smith, M R and Stacey, D W (1985) Nature 313, 241–243PubMedCrossRefGoogle Scholar
  19. Paris, S and Pouyssegur, J (1986) EMBO J. 5, 55–60PubMedGoogle Scholar
  20. Parrier, G., Hoebel, R and Racker, E (1986) Proc. Natl. Acad. Sci. 84, 2648–2652CrossRefGoogle Scholar
  21. Spat, A., Bradford, P G, McKinney, J S, Rubin, R P and Putney, J W Jr. (1986) Nature 319, 514–516PubMedCrossRefGoogle Scholar
  22. Sugimoto, Y., Whitman, M., Cantley, L C and Erickson, R L (1984) Proc. Natl. Acad. Sci. 81, 2117–2121PubMedCrossRefGoogle Scholar
  23. Taylor, C W and Merritt, J E (1986) Trends Pharmacol. Sci. 7, 238–242CrossRefGoogle Scholar
  24. Wakelam, M J O, Davies S A, Houslay, M D, McKay, I., Marshall, C J and Hall, A (1986) Nature 323, 173–176PubMedCrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1989

Authors and Affiliations

  • Colin W. Taylor
    • 1
  1. 1.Department of ZoologyUniversity of CambridgeCambridgeUK

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