Abstract
THE mitogen-activated protein (MAP) kinases Erk-1 and Erk-2 are proline-directed kinases that are themselves activated through concomitant phosphorylation of tyrosine and threonine residues1–4. The kinase p54 (Mr 54,000), which was first isolated from cycloheximide-treated rats, is proline-directed like Erks-1/2, and requires both Tyr and Ser/Thr phosphorylation3,5,6 for activity. p54 is, however, distinct from Erks-1/2 in its substrate specificity, being unable to phosphon late pp90rsk but more active in phosphor-ylating the c-Jun transactivation domain5,7,8. Molecular cloning of p54 reveals a unique subfamily of extracellularly regulated kinases. Although they are 40–45% identical in sequence to Erks-1/2, unlike Erks-1/2 the p54s are only poorly activated in most cells by mitogens or phorbol esters. However, p54s are the principal c-Jun N-terminal kinases activated by cellular stress and tumour necrosis factor (TNF)-α, hence they are designated stress-activated protein kinases, or SAPKs. SAPKs are also activated by sphingo-myelinase, which elicits a subset of cellular responses to TNF-α (ref. 9). SAPKs therefore define a new TNF-α and stress-activated signalling pathway, possibly initiated by sphingomyelin-based second messengers, which regulates the activity of c-Jun.
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References
Boulton, T. G. et al. Cell 65, 663–675 (1991).
Alvarez, E. et al. J. biol. Chem. 266, 15277–15285 (1991).
Mukhopadhyay, N. K. et al. J. biol. Chem. 267, 3325–3335 (1992).
Anderson, N. G., Maller, J. L., Tonks, N. K. & Sturgill, T. W. Nature 343, 651–653 (1990).
Kyriakis, J. M. & Avruch, J. J. biol. Chem. 265, 17355–17363 (1990).
Kyriakis, J. M., Brautigan, D. L., Ingebritsen, T. S. & Avruch, J. J. blol. Chem. 266, 10043–10046 (1991).
Pulverer, B. J. et al. Nature 353, 670–673 (1992).
Sturgill, T. W., Ray, L. B., Erikson, E. & Maller, J. L. Nature 334, 715–718 (1988).
Hannun, Y. A. J. biol. Chem. 269, 3125–3128 (1994).
Hanks, S. K., Quinn, A. M. & Hunter, T. Science 241, 42–52 (1988).
Courchesne, W. E., Kunisawa, R. & Thorner, J. Cell 58, 1107–1119 (1989).
Brewster, J. L. et al. Science 259, 1760–1763 (1993).
Levin, D. E. & Errede, B. A. J. NIH Res. 5, 49–52 (1993).
Elion, E. A., Grisafi, P. L. & Fink, G. R. Cell 60, 649–664 (1990).
Payne, D. M. et al. EMBO J. 10, 885–892 (1991).
Ahn, N. G. et al. J. blol. Chem. 266, 4220–4227 (1991).
Gómez, N. & Cohen, P. Nature 253, 170–173 (1991).
Nakielny, S., Cohen, P., Wu, J. & Sturgill, T. W. EMBO J. 11, 2123–2129 (1992).
Beutler, B. & Cerami, A. A. Rev. Biochem. 57, 505–517 (1988).
Goeddel D. V. et al. Cold Spring Harbor Symp. quant. Biol. 51, 597–609 (1986).
Brenner, D. A. et al. Nature 337, 661–663 (1989).
Binétruy, B., Smeal, T. & Karin, M. Nature 351, 122–127 (1991).
Smeal, T. et al. Nature 354, 494–496 (1991).
Adler, V., Franklin, C. C. & Kraft, A. S. Proc. natn. Acad. Sci. U.S.A. 89, 5341–5345 (1992).
Hibi, M. et al. Genes Dev. 7, 2135–2148 (1993).
Kyriakis, J. M. & Avruch, J. in Frontiers in Molecular Biology (ed. Woodgett, J. R.) (Oxford University Press, London, in the press).
Devary, Y., Gottleib, R., Smeal, T. & Karin, M. Cell 71, 1081–1091 (1992).
Pulverer, B. J. et al. Oncogene 8, 407–415 (1993).
Dressler, K. A., Mathias, S. & Kolesnik, R. N. Science 255, 1715–1718 (1992).
Kyriakis, J. M. et al. Nature 358, 417–421 (1992).
Dérijard, B. et al. Cell 76, 1025–1037 (1994).
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Kyriakis, J., Banerjee, P., Nikolakaki, E. et al. The stress-activated protein kinase subfamily of c-Jun kinases. Nature 369, 156–160 (1994). https://doi.org/10.1038/369156a0
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DOI: https://doi.org/10.1038/369156a0
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