1992 Nobel Prize in Physiology or Medicine, with fellow Biochemistry Professor Edmond Fischer [LINK!]
Ed Krebs’ work concerned the mechanisms involved in the intracellular transmission of hormone and growth factor signals. Of particular interest were mechanisms that involve the phosphorylation and dephosphorylation of proteins. One specific area of research addressed the question of how growth factor receptors possessing protein tyrosine kinase activity, e.g., the insulin, epidermal growth factor, and the platelet-derived growth factor receptors, regulate the phosphorylation of cellular proteins on serine or threonine residues. For example, could it be shown that protein serine/threonine kinases or phosphatases are direct targets for the receptors and undergo changes in enzymic activity as a result of phosphorylation on tyrosine residues or are indirect mechanisms involved? The group was also interested in the action of oncogene-encoded protein tyrosine kinases, and many of the same questions that were posed with respect to receptor-type kinases were also being asked with respect to these enzymes. Cells that are overexpressing “oncoproteins” with tyrosine kinase activity often display elevated protein serine/threonine kinase activity. Through identification of the specific enzymes involved it was hoped that some light coul be shed on the oncogenic process. More than a hundred different protein kinases have been identified in eukaryotic cells; and although it has been assumed that all of these enzymes are involved in regulatory processes, the functions of some of them remain obscure. One kinase in this category is casein kinase II, which Ed’s group investigated. Its functions and regulation were being studied by overexpression, through examining its biochemical properties, and by measuring its enzymic activity after treating cells with various drugs and hormones.
Graves, L.M., Northrop, J.L., Potts, B.C., Krebs, E.G. and Kimelman, D. (1993) FGF, but not activin, activates mitogen-activated protein kinase in Xenopus explants. Proc. Natl. Acad. Sci. USA, 91, 1662.
Seger, R., Seger, D., Reszka, A., Munar, E.S., Eldar-Finkelman, H., Dobrowolska, G., Jensen, A.M., Campbell, J.S., Fischer, E.H. and Krebs, E.G. (1994) Overexpression of mitogen-actvated protein kinase kinase (MAPKK) and its mutants in NIH 3T3 cells. J. Biol. Chem., 269, 25699.
Eldar-Finkelman, H., Seger, R., Vandenheede, J.R., and Krebs, E.G. (1995) Inactivation of glycogen synthase kinase-3 by EGF is mediated by RSK-MAPK signaling pathway in NIH/3T3 cells. J. Biol. Chem., 270, 987.
Campbell, J.S., Wenderoth, M.P., Hauschka, S.D., and Krebs, E.G. (1995) Differential activation of mitogen-activated protein kinase in response to basic fibroblast growth factor in skeletal muscle cells. Proc. Natl. Acad. Sci. USA, 92, 870.