Abstract
INTRACELLULAR signalling from receptor tyrosine kinases in mammalian cells involves the activation of a signal cascade which includes p21ras and the protein kinases p74raf-1, MAP kinase kinase and MAP kinases1–8. In the yeasts Schizosaccharomyces pombe and Saccharomyces cerevisiae the response to mating pheromones requires the Spkl and KSS1/FUS3 kinases, which have sequence homology to vertebrate MAP kinases9–12. The recent cloning of complementary DNAs for mammalian13–15 and frog16 MAP kinase kinases has shown that they are homologous to the S. pombe Byr1 (ref. 17) and S. cerevisiae STE7 (ref. 18) kinases, which have been proposed to function upstream of Spk1 and KSS1/FUS3, respectively19–22. We have investigated whether these apparently similar kinase pathways are functionally conserved between vertebrates and S. pombe. We report here that expression of mammalian MAP kinase kinase alone fails to complement a byr1 mutant of S. pombe. When coexpressed with Raf kinase, however, MAP kinase kinase is activated by phosphorylation and the mating defect of the byr1 mutant is rescued. This suggests that the pathways are functionally homologous and that Raf kinase may directly phosphorylate and activate MAP kinase kinase.
Similar content being viewed by others
References
Troppmair, J. et al. Oncogene 7, 1867–1873 (1992).
Leevers, S. J. & Marshall, C. J. EMBO J. 11, 569–574 (1992).
Thomas, S. M., DeMarco, M., D'Arcangelo, G., Halegoua, S. & Brugge, J. S. Cell 68, 1031–1040 (1992).
Wood, K. W., Sarnecki, C., Roberts, T. M. & Blenis, J. Cell 68, 1041–1050 (1992).
de Vries Smits, A. M. M., Burgering, B. M. T., Leevers, S. J., Marshall, C. J. & Bos, J. L. Nature 357, 602–604 (1992).
Kyriakis, J. M. et al. Nature 358, 417–121 (1992).
Howe, L. R. et al. Cell 71, 335–342 (1992).
Dent, P. et al. Science 257, 1404–1407 (1992).
Toda, T., Shimanuki, M. & Yanagida, M. Genes Dev. 5, 60–73 (1991).
Courchesne, W. E., Kunisawa, R. & Thorner, J. Cell 58, 1107–1119 (1989).
Elion, E. A., Grisafi, P. L. & Fink, G. R. Cell 60, 649–664 (1990).
Elion, E. A., Brill, J. A. & Fink, G. R. Proc. natn. Acad. Sci. U.S.A. 88, 9392–9396 (1991).
Ashworth, A., Nakielny, S., Cohen, P. & Marshall, C. Oncogene 7, 2555–2556 (1992).
Crews, C. M., Alessandrini, A. & Erikson, R. Science 258, 478–480 (1992).
Seger, R. et al. J. biol. Chem. 267, 25628–25631 (1993).
Kosako, H., Nishida, E. & Gotoh, Y. EMBO J. 12, 787–794 (1993).
Nadin-Davis, S. A. & Nasim, A. EMBO J. 7, 985–993 (1988).
Teague, M. A., Chaleff, D. T. & Errede, B. Proc. natn. Acad. Sci. U.S.A. 83, 7371–7375 (1986).
Neiman, A. M. et al. Molec. biol. Cell 4, 107–120 (1993).
Gotoh, Y. et al. Molec. cell. Biol. (in the press).
Gartner, A., Nasmyth, K. & Ammerer, G. Genes Dev. 6, 1280–1292 (1992).
Errede, B., Gartner, A., Zhou, Z., Nasmyth, K. & Ammerer, G. Nature 362, 261–265 (1993).
Gómez, N. & Cohen, P. Nature 353, 170–173 (1991).
Nakielny, S., Cohen, P., Wu, J. & Sturgill, T. W. EMBO J. 11, 2123–2129 (1992).
Traverse, S., Gómez, N., Paterson, H., Marshall, C. & Cohen, P. Biochem. J. 288, 351–355 (1992).
Matsuda, S., Gotoh, Y. & Nishida, E. J. biol. Chem. 268 3277–3281 (1993).
Roberts, T. M. Nature 360, 534 (1992).
Wang, Y., Xu, H.-P., Riggs, M., Rodgers, L. & Wigler, M. Molec. cell. Biol. 11, 3554–3563 (1991).
Styrkarsdottir, U., Egel, R. & Nelsen, O. Molec. gen. Genet. 235, 122–130 (1992).
Lange-Carter, C. A. et al. Science 260, 315–319 (1993).
Basi, G., Schmidt, E. & Maundrell, K. Gene 123, 130–136 (1993).
Egel, R. Planta 98, 89–91 (1971).
Moreno, S., Klar, A. & Nurse, P. Meth. Enzym. 194, 795–823 (1991).
Grimm, C., Kohli, J., Murray, J. & Maundrell, K. Molec. gen. Genet. 215, 81–86 (1988).
Boyle, W. J., Van der Geer, P. & Hunter, T. Meth. Enzym. 201, 110–149 (1991).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hughes, D., Ashworth, A. & Marshall, C. Complementation of byrl in fission yeast by mammalian MAP kinase kinase requires coexpression of Raf kinase. Nature 364, 349–352 (1993). https://doi.org/10.1038/364349a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/364349a0
- Springer Nature Limited
This article is cited by
-
Manganese SOD Mimics Are Effective Against Heat Stress in a Mutant Fission Yeast Deficient in Mitochondrial Superoxide Dismutase
Biological Trace Element Research (2011)
-
Sequential activation of MAP kinase cascade by angiotensin II in opossum kidney cells
Kidney International (1995)
-
Yeast Srp1, a nuclear protein related toDrosophila and mouse pendulin, is required for normal migration, division, and integrity of nuclei during mitosis
Molecular and General Genetics MGG (1995)
-
Signal transduction pathways involving the raf proto-oncogene
Cancer and Metastasis Reviews (1994)
-
The pathway to signal achievement
Nature (1993)