Abstract
The reversible phosphorylation of proteins is central to the regulation of most aspects of cell function but, even after the first protein kinase was identified, the general significance of this discovery was slow to be appreciated. Here I review the discovery of protein phosphorylation and give a personal view of the key findings that have helped to shape the field as we know it today.
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References
MacKintosh, C., Beattie, K. A., Klumpp, S., Cohen, P. & Codd, G. A. FEBS Lett 264, 187–192 (1990).
Cori, G. T. & Green, A. A. J. Biol. Chem. 151, 31–38 (1943).
Burnett, G. & Kennedy, E. P. J. Biol. Chem. 211, 969–980 (1954).
Fischer, E. H. & Krebs, E. G. J. Biol. Chem. 216, 121–132 (1955).
Krebs, E. G. & Fischer, E. H. Biochim. Biophys. Acta 20, 150–157 (1956).
Sutherland, E. W. & Wosilait, W. D. Nature 175, 169–170 (1955).
Fischer, E. H., Graves, D. J., Crittenden, E. R. S. & Krebs, E. G. J. Biol. Chem. 234, 1698–1704 (1959).
Ingebritsen, T. S. & Cohen, P. Eur. J. Biochem. 132, 255–261 (1983).
Robison, G. A., Butcher, R. W. & Sutherland, E. W. Cyclic AMP Academic Press, London (1971).
Walsh, D. A., Perkins, J. P. & Krebs E. G. J. Biol. Chem. 243, 3763–3765 (1968).
Bishop, J. S. & Larner, J. Biochim. Biophys. Acta 171, 374–377 (1969).
Soderling, T. R. et al. J. Biol. Chem. 245, 6617–6628 (1970).
Heilmeyer, L. M. G. Jr, Meyer, F., Haschke, R. H. & Fischer, E. H. J. Biol. Chem. 245, 6649–6656 (1970).
Brostrom, C. O., Hunkeler, F. L. & Krebs, E. G. J.Biol. Chem. 246, 1961–1967 (1971).
Cohen, P., Burchell, A., Foulkes, J. G. & Cohen, P. T. W. FEBS Lett. 92, 287–292 (1978).
Linn, T. C., Pettit, F. H. & Reed, L. J. Proc. Natl Acad. Sci. USA 62, 234–241 (1969).
Corbin, J. D., Reimann, E. M., Walsh, D. A. & Krebs, E. G. J. Biol. Chem. 245, 4849–4851 (1970).
Ljungstrom, O., Hjelmqvist, G. & Engstrom, L. Biochim. Biophys. Acta 358, 289–298 (1974).
Kuo, J. F. & Greengard, P. Proc. Natl Acad. Sci. USA 64, 1349–1355 (1969).
England, P. J. FEBS Lett. 50, 57–60 (1975).
Tada, M., Kirschberger, M. A. & Katz, A. M. J. Biol. Chem. 250, 2640–2647 (1975).
Langan, T. A. Proc. Natl Acad. Sci. USA 64, 1276–1283 (1969).
Dabrowska, R., Sherry, J. M. F., Aromatorio, D. K. & Hartshorne, D. J. Biochemistry 17, 253–258 (1978).
Schulman, H. & Greengard, P. Nature 271, 478–479 (1978).
McGuinness, T. L., Lai, Y., Greengard, P., Woodgett, J. R. & Cohen, P. FEBS Lett. 163, 329–334 (1983).
Kishimoto, A., Takai, Y., Mori, T., Kikkawa, U. & Nisdhizuka, Y. J. Biol. Chem. 255, 2273–2276 (1980).
Stewart, A. A., Ingebritsen, T. S., Manalan, A., Klee, C. B. & Cohen, P. FEBS Lett. 137, 80–84 (1982).
Liu, J., Farmer, J. D., Lane, W. S., Friedman, J., Weissman, I. & Schreiber, S. L. Cell 66, 807–815 (1991).
Daile, P. & Carnegie, P. R. & Young, J. D. Nature 257, 416–418 (1975).
Zetterqvist, O., Ragnarsson, U., Humble, E., Berglund, L. & Engstrom, L. Biochem. Biophys. Res. Commun. 70, 696–703 (1976).
Kemp, B. E., Benjamini, E. & Krebs, E. G. Proc. Natl. Acad. Sci. USA 73, 1038–1042 (1976).
Shoji, S. et al. Proc. Natl Acad. Sci. USA 78, 848–851 (1981).
Nurse, P. Trends Genet. 1, 51–55 (1985).
Cohen, P. Trends Biochem. Sci. 1, 38–40 (1976).
Nakielny, S., Campbell, D. G. & Cohen, P. Eur. J. Biochem. 199, 713–722 (1991).
Stralfors, P., Hiraga, A. & Cohen, P. Eur. J. Biochem. 149, 295–303 (1985).
Bregman, D. B., Bhattacharyya, N, and Rubin, C. S. J. Biol. Chem. 266, 4648–4656 (1989).
Colledge, M. & Scott, M. D. Trends Cell Biol. 9, 216–221 (1999).
Collett, M. S. & Erikson, R. L. Proc. Natl Acad. Sci. USA 75, 2021–2024 (1978).
Hunter, T. & Sefton, B. M. Proc. Natl Acad. Sci. USA 77, 1311–1315 (1980).
Ushiro, H. & Cohen, S. J. Biol. Chem. 255, 8363–8365 (1980).
Kasuga, M., Karlsson, F. A. & Kahn, C. R. Science 215, 185–187 (1982).
Sadowski, I., Stone, J. C. & Pawson, T. Mol. Cell. Biol. 6, 4396–4408 (1986).
Anderson, A., Koch, C. A., Grey, L., Ellis, C., Moran, M. F. & Pawson, T. Science 250, 979–982 (1990).
Tonks, N. K., Diltz, C. D. & Fischer, E. H. J. Biol. Chem. 263, 6722–6730 (1988).
Tonks, N. K., Charbonneau, H., Diltz, C. D., Fischer, E. H. & Walsh, K. A. Biochemistry 27, 8695–8701 (1988).
Wilkes, A. F., Harpur, A. G., Kurban, R. R., Ralph, S. J., Zürcher, G. & Ziemiecki, A. Mol. Cell. Biol. 11, 2057–2065(1991).
Wilks, A. F. & Harpur, A. G. Bioessays 16, 313–320 (1994).
Ray, L. B. & Sturgill, T. W. Proc. Natl Acad. Sci. USA 84, 1502–1506 (1987).
Anderson, N., Maller, J. L., Tonks, N. K. & Sturgill, T. W. Nature 343, 651–653 (1990).
Ahn, N. G., Seger, R., Bratlien, R. L., Diltz, C. D., Tonks, N. K. & Krebs, E. G. J. Biol. Chem. 266, 4220–4227 (1991).
Gomez, N. & Cohen, P. Nature 353, 170–173 (1991).
Leevers, S. J. & Marshall, C. J. EMBO J. 11, 569–574 (1992).
Whitman, M., Downes, C. P., Keeler, M., Keller, T. & Cantley, L. C. Nature 332, 644–646 (1988).
Traynor-Kaplan, A. E., Harris, A. L., Thompson, B. L., Taylor, P. & Sklar, L. A. Nature 334, 353–356 (1988).
Toker, A. & Cantley, L. C. Nature 387, 673–676 (1997).
Vlahos, C. J., Matter, W. F., Hui, K. Y. & Brown, R. F. J. Biol. Chem. 269, 5241–5248 (1994).
Ui, M., Okada, T., Hazeki, K. & Hazeki, O. Trends Biochem. Sci. 20, 303–307 (1995).
Franke, T. F. et al. Cell 81, 727–736 (1995).
Burgering, B. M. Th and Coffer, P. J. Nature 376, 599–602 (1995).
Cross, D. A. E., Alessi, D. R., Cohen, P., Anjelkovic, M. & Hemmings, B. A. Nature 378, 785–788 (1995).
Alessi, D. R. et al. Curr. Biol. 7, 261–269 (1997).
Cohen, P. Nature 296, 613–620 (1982).
Smith, D. L., Chen, C-C, Bruegger, B. B., Holtz, S. L., Halpern, R. M. & Smith, R. A. Biochemistry 13, 3780–3785 (1974).
Swanson, R. V., Alex, L.A. & Simon, M. I. Trends Biochem. Sci. 19, 439–518 (1994).
Levy-Favatier, F., Delpech, M. & Kruh, J. Eur. J. Biochem. 166, 617–621 (1987).
Khandelwahl, R. M., Mattoo, R. L. & Waygood, E. B. FEBS Lett. 162, 127–132 (1983).
Cohen, P. Nature Rev. Drug Disc. 1, 309–315 (2002).
Acknowledgements
This perspective is a personal account of some of the important events in protein phosphorylation research that have taken place over the past 50 years or more. I apologize to the scientists whose many important discoveries that could not be included or referenced in this article because of space restrictions. The work carried out in my laboratory is supported by the UK Medical Research Council, The Royal Society of London, Diabetes U.K., The Louis Jeantet Foundation, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, NovoNordisk and Pfizer.
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Cohen, P. The origins of protein phosphorylation. Nat Cell Biol 4, E127–E130 (2002). https://doi.org/10.1038/ncb0502-e127
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DOI: https://doi.org/10.1038/ncb0502-e127