Abstract
EUKARYOTIC cells respond to different extracellular stimuli by recruiting homologous signalling pathways that use members of the MEKK, MEK and ERK families of protein kinases. The MEKK→ MEK→ ERK core pathways of Saccharomyces cere-visiae may themselves be regulated by members of the STE20 family of protein kinases1,2. Here we report specific activation of the mammalian stress-activated protein kinase (SAPK) pathway by germinal centre kinase (GCK; ref. 3), a human STE20 homologue3,4. SAPKs, members of the ERK family, are activated in situ by inflammatory stimuli, including tumour-necrosis factor (TNF) and interleukin-1, and phosphorylate and probably stimulate the transactivation function of c-Jun5-7. Although GCK is found in many tissues, its expression in lymphoid follicles is restricted to the cells of the germinal centre, where it may participate in B-cell differentiation3. Activation of the SAPK pathway by GCK illustrates further the striking conservation of eukaryotic signalling mechanisms and defines the first physiological function of a mammalian Ste20.
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References
Levin, D. E. & Errede, B. Curr. Opin. Cell Biol. 7, 197–202 (1995).
Herskowitz, I. Cell 80, 187–197 (1995).
Katz, P., Whalen, G. & Kehrl, J. H. J. biol. Chem. 269, 16802–16809 (1994).
Leberer, E. et al. EMBO J. 11, 4815–4824 (1992).
Kyriakis, J. M. et al. Nature 369, 156–160 (1994).
Dérijard, B. et al. Cell 76, 1025–1037 (1994).
Sánchez, I. et al. Nature 372, 794–798 (1994).
Han, J., Lee, J.-D., Bibbs, L. & Ulevitch, R. J. Science 265, 808–811 (1994).
Avruch, J., Zhang, X.-f. & Kyriakis, J. M. Trends biochem. Sci. 19, 279–283 (1994).
Cowley, S., Paterson, H., Kemp, P. & Marshall, C. J. Cell 77, 841–852 (1994).
Mansour, S. J. et al. Science 265, 966–970 (1994).
Rouse, J. et al. Cell 78, 1027–1037 (1994).
Freshney, N. W. et al. Cell 78, 1039–1049 (1994).
Choi, K.-Y., Scatterberg, B., Lyons, D. M. & Elion, E. A. Cell 78, 499–512 (1994).
Dérijard, B. et al. Science 267, 682–685 (1995).
Yan, M. et al. Nature 372, 798–800 (1994).
Manser, E. et al. Nature 367, 40–46 (1994).
Martin, G. A., Bollag, G., McCormick, F. & Abo, A. EMBO J. 14, 1970–1978 (1995).
Freisen, H., Lunz, R., Doyle, S. & Segall, J. Genes Dev. 8, 2162–2175 (1994).
Coso, O. A. et al. Cell 81, 1137–1146 (1995).
Minden, A. et al. Cell 81, 1147–1157 (1995).
Bruder, J. T., Heidecker, G. & Rapp, U. R. Genes Dev. 6, 545–556 (1992).
Lee, J. C. et al. Nature 372, 739–746 (1994).
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Pombo, C., Kehrl, J., Sánchez, I. et al. Activation of the SAPK pathway by the human STE20 homologue germinal centre kinase. Nature 377, 750–754 (1995). https://doi.org/10.1038/377750a0
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DOI: https://doi.org/10.1038/377750a0
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