Advanced Research on Animal Cell Technology pp 187-200 | Cite as
Phosphoinositide metabolism and control of cell proliferation
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 EnzymePreview
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References
- Bar-Sagi, D and Feramisco, J R (1986) Science 233, 1061–1068PubMedCrossRefGoogle Scholar
- Berridge, M J and Irvine, R F (1984) Nature 312, 315–321PubMedCrossRefGoogle Scholar
- Berridge, M J, Brown, K D, Irvine, R F and Heslop, J P (1985) J. Cell Sci. Suppl 3, 187–198Google Scholar
- Brass, L F and Joseph S K (1985) J. Biol. Chem. 260, 15172–15179PubMedGoogle Scholar
- Chambard, J C, Paris, S., L’Allemain, G and Pouyssegur, J (1987) Nature 326, 800–803PubMedCrossRefGoogle Scholar
- Clapper, D L and Lee, H C (1985) J. Biol. Chem. 260, 13947–13954PubMedGoogle Scholar
- Fleischman, L F, Chahwala, S B and Cantley, L (1986) Science 231, 407–410PubMedCrossRefGoogle Scholar
- 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
- Heslop, J P, Blakeley, D M, Brown, K D, Irvine, R F and Berridge, M J (1986) Cell 47, 703–709PubMedCrossRefGoogle Scholar
- Irvine, R F and Moor, R M (1986) Biochem. J. 240, 917–920PubMedGoogle Scholar
- Letterio, J., Coughlin, S and Williams, L (1986) Science 234, 1117–1119PubMedCrossRefGoogle Scholar
- Lopez-Rivas, A., Mendoza, S A, Nanberg, E., Sinnett-Smith, J W and Rozengurt, E (1987) Proc. Natl. Acad. Sci. 84, 5768–5772PubMedCrossRefGoogle Scholar
- Macara, I G, Marinetti, G V and Baldozzi, P C (1984) Proc. Natl. Acad. Sci. 81, 2778–2732CrossRefGoogle Scholar
- Macdonald, M L, Kuenzel, E A, Glomset, J A and Krebs, E G (1985) Proc. Natl. Acad. Sci. 82, 3993–3997PubMedCrossRefGoogle Scholar
- Micheli, R H (1982) Cell Calcium 3, 429–440CrossRefGoogle Scholar
- Moolenaar, W H, Tertoolen, L G J and de Laat, S W (1984) Nature 312, 371–374PubMedCrossRefGoogle Scholar
- Moolenaar, W H, Kruiger, W., Tilly, B C, Verlaan, I., Bierman, A J and de Laat S W (1986) Nature 323, 171–173PubMedCrossRefGoogle Scholar
- Mulcahy, L S, Smith, M R and Stacey, D W (1985) Nature 313, 241–243PubMedCrossRefGoogle Scholar
- Paris, S and Pouyssegur, J (1986) EMBO J. 5, 55–60PubMedGoogle Scholar
- Parrier, G., Hoebel, R and Racker, E (1986) Proc. Natl. Acad. Sci. 84, 2648–2652CrossRefGoogle Scholar
- Spat, A., Bradford, P G, McKinney, J S, Rubin, R P and Putney, J W Jr. (1986) Nature 319, 514–516PubMedCrossRefGoogle Scholar
- Sugimoto, Y., Whitman, M., Cantley, L C and Erickson, R L (1984) Proc. Natl. Acad. Sci. 81, 2117–2121PubMedCrossRefGoogle Scholar
- Taylor, C W and Merritt, J E (1986) Trends Pharmacol. Sci. 7, 238–242CrossRefGoogle Scholar
- Wakelam, M J O, Davies S A, Houslay, M D, McKay, I., Marshall, C J and Hall, A (1986) Nature 323, 173–176PubMedCrossRefGoogle Scholar