Abstract
PLATELET-DERIVED growth factor receptor (PDGF-R) phosphory-lation at tyrosines 740/751 and insulin receptor phosphorylation of insulin receptor substrate-1 effects the recruitment and activation of phosphatidylinositol-3-OH kinase (PIK)1–5. Changes in PI(3)K activity correlate with cell growth but its downstream signal transducers are unknown4,5. Activation of the 70/85K S6 kinases (pp70S6k) by serine phosphorylation6,7 results in 40S ribosomal protein S6 phosphorylation and is important for Gl cell-cycle transition in a variety of cells8–11. Although receptor tyrosine kinases activate the microtubule-associated protein kinase cascade through SH2-/SH3-adaptor proteins, Sos and c-Ras12, it is unclear how tyrosine kinases are coupled to the pp70S6k phosphorylation cascade. Here we report that PI(3)K mediates PDGF or insulin receptor signalling to pp70S6k. PI(3)K-mediated activation of pp70S6k is independent of conventional protein kinase C isoforms. Additionally, rapamycin blocks pp70S6k activation by all mitogens8–10, without inhibiting PI(3)K, and acts downstream in this signalling system.
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References
Kazlauskas, A., Kashishian, A., Cooper, J. A. & Valius, M. Molec. cell. Biol. 12, 2534–2544 (1992).
Fantl, W. J. et al. Cell 69, 413–423 (1992).
Sun, X. J. et al. Nature 352, 73–77 (1991).
Carpenter, C. L. & Cantley, L. C. Biochemistry 29, 11147–11156 (1990).
Parker, P. J. & Waterfield, M. D. Cell Growth Differ. 3, 747–752 (1992).
Banerjee, P. et al. Proc. natn. Acad. Sci. U.S.A. 87, 8550–8554 (1990).
Ferrari, S. et al. Prac. natn. Acad. Sci. USA. 89, 7282–7286 (1992).
Chung, J., Kuo, C. J., Crabtree, G. R. & Blenis, J. Cell 69, 1227–1236 (1992).
Kuo, C. J. et al. Nature 358, 70–74 (1992).
Price, D. J. et al. Science 257, 973–977 (1992).
Lane, H. A., Fernandez, A., Lamb, N. J. C. & Thomas, G. Nature 363, 170–172 (1993).
Blenis, J. Proc. natn. Acad. Sci. U.S.A. 90, 5889–5892 (1993).
Valius, M. & Kazlauskas, A. Cell 73, 321–334 (1993).
Erikson, R. L. J. biol. Chem. 266, 6007–6010 (1991).
Ruderman, N. B., Kappeller, R., White, M. F. & Cantley, L. C. Proc. natn. Acad. Sci. U.S.A. 87, 1411–1415 (1990).
Nishibe, S. et al. Proc. natn. Acad. Sci. U.S.A. 87, 424–428 (1990).
Kanai, F. et al. Biochem. biophys. Res. Commun. 195, 762–768 (1993).
Yano, H. et al. J. biol. Chem. 268, 25846–25856 (1993).
Arcaro, A. & Wymann, M. P. Biochem. J. 296, 297–301 (1993).
Vlahos, C. J. et al. J. biol. Chem. 269, 5241–5248 (1994).
Cheatham, B. et al. Molec. cell. Biol. (in the press).
Susa, M., Vulevic, D., Lane, H. A. & Thomas, G. J. biol. Chem. 267, 6905–6909 (1992).
Nishimura, R. et al. Molec. cell. Biol. 13, 6889–6896 (1993).
Nakanishi, H. N. et al. J. biol. Chem. 268, 13–16 (1993).
Sutherland, C., Leighton, I. A. & Cohen, P. Biochem. J. 296, 15–19 (1993).
Boyle, W. B. et al. Cell 64, 573–584 (1991).
Tsai, M. et al. Eur. J. Immun. 23, 3286–3291 (1993).
Fingar, D. C., Hausdorff, S. F., Blenis, J. & Birnbaum, M. J. J. biol. Chem. 268, 3005–3008 (1993).
Grove, J. R. et al. Molec. cell. Biol. 11, 5541–5550 (1991).
Whitman, M. et al. Nature 315, 239–242 (1985).
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Chung, J., Grammar, T., Lemon, K. et al. PDGF- and insulin-dependent pp70S6k activation mediated by phosphatidylinositol-3-OH kinase. Nature 370, 71–75 (1994). https://doi.org/10.1038/370071a0
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DOI: https://doi.org/10.1038/370071a0
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