Abstract
MANY growth factors upon stimulation of their receptors induce the activity of extracellular signal-regulated kinases, ERKs, also known as MAP kinases1,2. Several of these growth factors also activate the ras proto-oncogene product, p21ras (Ras), by stimulating the conversion of the inactive GDP-bound form of Ras to the active GTP-bound form3–6. We have shown that direct introduction of p21ras oncoprotein into cells in the absence of growth factors activates ERKs within five minutes7, which indicates that normal p21ras may be involved in the activation of ERKs by growth factors. Here we use a recombinant vaccinia virus expressing an interfering mutant of p21ras, RasAsn17, to investigate this question. In NIH3T3 cells that overexpress the insulin receptor, this recombinant virus inhibits insulin-induced activation of ERK2 completely, but there is no inhibition of insulin-induced activation of phosphatidyl-inositol-3-kinase. In rat-1 cells the recombinant virus inhibited ERK2 activity induced by platelet-derived growth factor (PDGF) but not by phorbol ester. We conclude that p21ras mediates insulin-and PDGF-induced activation of ERK2.
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References
Ray, L. B. & Sturgill, T. W. Proc. natn. Acad. Sci. U.S.A. 84, 1502–1506 (1987).
Cobb, M. H., Boulton, T. G. & Robbins, D. J. Cell Reg. 2, 965–978 (1991).
Burgering, B. M. T. et al. EMBO J. 10, 1103–1109 (1991).
Downward, J., Graves, J. D., Warne, P. H., Rayter, S. & Cantrell, D. A. Nature 346, 719–723 (1990).
Gibbs, J. B., Marshall, M. S., Scolnick, E. M., Dixon, R. A. F. & Vogel, U. S. J. biol. Chem. 265, 20437–20442 (1990).
Satoh, T., Endo, M., Nakafuku, M., Makamura, S. & Kaziro, Y. Proc. natn. Acad. Sci. U.S.A. 87, 5993–5997 (1990).
Leevers, S. J. & Marshall, C. J. EMBO J. 11, 569–574 (1992).
Anderson, N. G., Maller, J. L., Tonks, N. K. & Sturgill, T. W. Nature 343, 651–653 (1990).
Farnsworth, C. L. & Feig, L. A. Molec. cell. Biol. 11, 4822–4829 (1991).
Stacey, D. W. et al. Oncogene 6, 2297–2304 (1991).
Medema, R. H., Wubbolts, R. & Bos, J. L. Molec. cell. Biol. 11, 5963–5967 (1991).
Sjölander, A., Yamamoto, K., Huber, B. E. & Lapetina, E. G. Proc. natn. Acad. Sci. U.S.A. 88, 7908–7912 (1991).
Blackshear, P. J., Haupt, D. M. & Stumpo, D. J. J. biol. Chem. 266, 10946–10952 (1991).
Cantley, L. C. et al. Cell 64, 281–302 (1991).
Gómez, N. & Cohen, P. Nature 353, 170–173 (1991).
Dent, P. et al. Nature 348, 302–308 (1990).
Pulverer, B. J., Kryakis, J. M., Avruch, J., Nikolakaki, E. & Woodgett, J. R. Nature 353, 670–674 (1991).
Binétruy, B., Smeal, T. & Karin, M. Nature 351, 122–127 (1991).
Medema, R. H., Burgering, B. M. T. & Bos, J. L. J. biol. Chem. 266, 21186–21189 (1991).
Davison, A. J. & Moss, B. J. molec. Biol. 210, 749–769 (1989).
Mackett, M., Smith, G. L. & Moss, B. in DNA Cloning: A Practical Approach (II) (ed. Glover, D. M.) 191–211 (IRL, Oxford, 1985).
Sturgill, T. W., Ray, L. B., Erikson, E. & Mailer, J. Nature 334, 715–718 (1988).
Osterop, A. P. R. M. et al. J. biol. Chem. (in the press).
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de Vries-Smits, A., Burgering, B., Leevers, S. et al. Involvement of p21ras in activation of extracellular signal-regulated kinase 2. Nature 357, 602–604 (1992). https://doi.org/10.1038/357602a0
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DOI: https://doi.org/10.1038/357602a0
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