Abstract
The sensitivity to regulation of proteins undergoing covalent modification can be greatly increased when the substrates saturate the converter enzymes. This phenomenon, termed zero-order ultrasensitivity, has been found to occur in the reversible phosphorylation of isocitrate dehydrogenase. The possibility that this enhanced sensitivity is a common feature of covalent regulatory systems is discussed.
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References
Krebs, E. G. & Beavo, J. A. A. Rev. Biochem. 48, 923–959 (1979).
Weller, M. Protein Phosphorylation (Pion, London, 1979).
Chock, P. B., Rhee, S. G. & Stadtman, E. R. A. Rev. Biochem. 49, 813–843 (1980).
Colett, M. S. & Erikson, R. L. Proc. natn. Acad. Sci. U.S.A. 75, 2021–2024 (1978).
Levinson, A. D., Oppermann, H., Levintow, L., Varmus, H. E. & Bishop, J. B. Cell 15, 561–572 (1978).
Cohen, S., Ushiro, H., Stoscheck, C. & Chinkers, M. J. biol. Chem. 257, 1523–1531 (1982).
Kasuga, M., Zick, Y., Blithe, A. L., Crettaz, M. & Kahn, C. R. Nature 298, 667–669 (1982).
Roth, R. A. & Cassell, D. J. Science 219, 299–301 (1983).
Goldbeter, A. & Koshland, D. E. Jr Proc. natn. Acad. Sci. U.S.A. 78, 6840–6844 (1981).
Koshland, D. E. Jr, Goldbeter, A. & Stock, J. B. Science 217, 220–225 (1982).
Kornberg, H. L. & Madsen, N. B. Biochem. biophys. Acta 24, 651–653 (1957).
Bennett, P. M. & Holms, W. H. J. gen. Microbiol. 87, 37–51 (1975).
Garnak, M. & Reeves, H. C. Science 203, 1111–1112 (1979).
LaPorte, D. C. & Koshland, D. E. Jr Nature 300, 458–460 (1982).
Koshland, D. E. Jr, Nemethy, G. & Filmer, D. Biochemistry 5, 365 (1966).
Lowry, O. H., Carter, J., Ward, J. B. & Glaser, L. J. biol. Chem. 246, 6511–6521 (1971).
Nimmo, G. A. & Cohen, P. Eur. J. Biochem. 87, 353–365 (1978).
Fischer, E. H., Heilmeyer, L. M. G. & Haschke, R. H. Curr. Topics cell. Regulation 4, 221–251 (1971).
Bishop, J. M. Adv. Cancer Res. 37, 1–32 (1982).
Garnak, M. & Reeves, H. C. J. biol. Chem. 254, 7915–7920 (1979).
Reimann, E. M., Walsh, D. A. & Krebs, E. G. J. biol. Chem. 246, 1986–1995 (1971).
Dixon, M. Biochem. J. 55, 170–171 (1953).
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LaPorte, D., Koshland, D. Phosphorylation of isocitrate dehydrogenase as a demonstration of enhanced sensitivity in covalent regulation. Nature 305, 286–290 (1983). https://doi.org/10.1038/305286a0
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DOI: https://doi.org/10.1038/305286a0
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