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A brain serine/threonine protein kinase activated by Cdc42 and Rac1

Abstract

A new brain serine/threonine protein kinase may be a target for the p21ras-related proteins Cdc42 and Rac1. The kinase sequence is related to that of the yeast protein STE20, implicated in pheromone-response pathways. The kinase complexes specifically with activated (GTP-bound) p21, inhibiting p21 GTPase activity and leading to kinase autophosphorylation and activation. Autophosphorylated kinase has a decreased affinity for Cdc42/Rac, freeing the p21 for further stimulatory activities or downregulation by GTPase-activating proteins. This bimolecular interaction provides a model for studying p21 regulation of mammalian phosphorylation signalling pathways.

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References

  1. Bucci, C. et al. Cell 70, 715–728 (1992).

    Article  CAS  PubMed  Google Scholar 

  2. Sluijs, P. et al. Cell 70, 729–740 (1992).

    Article  PubMed  Google Scholar 

  3. Ridley, A. J. & Hall, A. Cell 70, 389–399 (1992).

    Article  CAS  PubMed  Google Scholar 

  4. Ridley, A. J., Paterson, H. F., Johnston, C. L., Diekmann, D. & Hall, A. Cell 70, 401–410 (1992).

    Article  CAS  PubMed  Google Scholar 

  5. Barbacid, M. Rev. Biochem. 56, 779–827 (1987).

    Article  CAS  Google Scholar 

  6. Wang, J., Suzuki, N. & Kataoka, T. Molec. cell. Biol. 12, 4937–4945 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Martin, G. A. et al. Science 255, 192–194 (1992).

    Article  ADS  CAS  PubMed  Google Scholar 

  8. Pazin, M. J. & Williams, L. T. Trends biochem. Sci. 17, 374–378 (1992).

    Article  CAS  PubMed  Google Scholar 

  9. Ahn, G. A., Seger, R. & Krebs, E. G. Curr. Opin. Cell Biol. 4, 992–999 (1992).

    Article  CAS  PubMed  Google Scholar 

  10. Manser, E. et al. J. biol. Chem. 267, 16025–16028 (1992).

    CAS  PubMed  Google Scholar 

  11. Johnson, D. I. & Pringle, J. R. J. Cell Biol. 111, 143–152 (1990).

    Article  CAS  PubMed  Google Scholar 

  12. Knaus, U. G., Heyworth, P. G., Evans, T., Curnette, J. T. & Bokoch, G. M. Science 254, 1512–1515 (1991).

    Article  ADS  CAS  PubMed  Google Scholar 

  13. Vincent, S., Jeanteur, P. & Fort, P. Molec. cell. Biol. 12, 3138–3148 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Diekmann, D. et al. Nature 351, 400–402 (1991).

    Article  ADS  CAS  PubMed  Google Scholar 

  15. Leung, T., How, B-E., Manser, E. & Lim, L. J. biol. Chem. 268, 3813–3816 (1993).

    CAS  PubMed  Google Scholar 

  16. Settleman, J., Albright, C. F., Foster, L. C. & Weinberg, R. A. Nature 359, 153–154 (1992).

    Article  ADS  CAS  PubMed  Google Scholar 

  17. Hall, A. Cell 69, 389–391 (1992).

    Article  CAS  PubMed  Google Scholar 

  18. Tsai, M-H., Hall, A. & Stacey, D. W. Molec. cell. Biol. 9, 5260–5264 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Menard, L. et al. Eur. J. Biochem. 206, 537–546 (1992).

    Article  CAS  PubMed  Google Scholar 

  20. Hart, M. J. et al. Science 258, 812–815 (1992).

    Article  ADS  CAS  PubMed  Google Scholar 

  21. Hart, M. J., Eva, A., Evans, T., Aaronson, A. & Cerione, R. A. Nature 354, 311–314 (1991).

    Article  ADS  CAS  PubMed  Google Scholar 

  22. Garrett, M. D., Self, A. J., van Oers, C. & Hall, A. J. biol. Chem. 264, 10–13 (1989).

    CAS  PubMed  Google Scholar 

  23. Manser, E., Leung, T., Salihuddin, H., Tan, L. & Lim, L. Nature 363, 364–367 (1993).

    Article  ADS  CAS  PubMed  Google Scholar 

  24. Leberer, E., Dignard, D., Harcus, D., Thomas, D. Y. & Whiteway, M. EMBO J. 11, 4815–4824 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ramer, S. W. & Davis, R. W. Proc. natn. Acad. Sci. U.S.A. 90, 452–456 (1993).

    Article  ADS  CAS  Google Scholar 

  26. Bollag, G. & McCormick, F. A. Rev. Cell Biol. 7, 601–632 (1991).

    Article  CAS  Google Scholar 

  27. Ferrell, J. E. & Martin, G. S. Molec. cell. Biol. 10, 3020–3026 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Didsbury, J., Weber, R. F., Bokoch, G. M., Evans, T. & Snyderman, R. J. biol. Chem. 264, 16378–16382 (1989).

    CAS  PubMed  Google Scholar 

  29. Munemitsu, S. et al. Molec. cell. Biol. 10, 5977–5982 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Doucet, J-P., Pierce, G. N., Hertzberg, E. L. & Tuana, B. S. J. biol. Chem. 267, 16503–16508 (1992).

    CAS  PubMed  Google Scholar 

  31. Regazzi, R., Kikuchi, A., Takai, Y. & Wollheim, C. B. J. biol. Chem. 267, 17512–17519 (1992).

    CAS  PubMed  Google Scholar 

  32. Mizuno, T. et al. Proc. natn. Acad. Sci. U.S.A. 88, 6442–6446 (1991).

    Article  ADS  CAS  Google Scholar 

  33. Pai, E. F. et al. EMBO J. 9, 2351–2359 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Self, A. J., Paterson, H. F. & Hall, A. Oncogene 8, 655–661 (1993).

    CAS  PubMed  Google Scholar 

  35. Hall, A. Science 249, 635–640 (1990).

    Article  ADS  CAS  PubMed  Google Scholar 

  36. Shiritaki, H. et al. Molec. cell. Biol. 13, 2061–2068 (1993).

    Article  Google Scholar 

  37. Steinberg, R. A., Cauthron, R. D., Symcox, M. M. & Shuntoh, H. Molec cell. Biol. 13, 2332–2341 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Payne, M. D. et al. EMBO J. 10, 885–892 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Grove, J. R. et al. Molec. cell. Biol. 11, 5541–5550 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Gross, E., Goldberg, D. & Levitzki, A. Nature 360, 762–765 (1992).

    Article  ADS  CAS  PubMed  Google Scholar 

  41. Roberts, T. M. Nature 360, 534–535 (1992).

    Article  ADS  CAS  PubMed  Google Scholar 

  42. Itoh, T. et al. Proc. natn. Acad. Sci. U.S.A. 90, 975–979 (1993).

    Article  ADS  CAS  Google Scholar 

  43. Moodie, S. A., Willumsen, B. M., Weber, M. J. & Wolfman, A. Science 260, 1658–1661 (1993).

    Article  ADS  CAS  PubMed  Google Scholar 

  44. Zhang, X-f. et al. Nature 364, 308–313 (1993).

    Article  ADS  CAS  PubMed  Google Scholar 

  45. Warne, P. H., Viciana, P. R. & Downward, J. Nature 364, 352–355 (1993).

    Article  ADS  CAS  PubMed  Google Scholar 

  46. Vojtek, A. B., Hollenberg, S. M. & Cooper, J. A. Cell 74, 205–214 (1993).

    Article  CAS  PubMed  Google Scholar 

  47. Schaller, M. D. et al. Proc. natn. Acad. Sci. U.S.A. 89, 5192–5196 (1992).

    Article  ADS  CAS  Google Scholar 

  48. Marsh, L., Neiman, A. M. & Herskovitz, I. Rev. Cell. Biol. 7, 699–728 (1991).

    Article  CAS  Google Scholar 

  49. Errede, B. & Levin, D. E. Curr. Opin. Cell. Biol. 5, 254–260 (1993).

    Article  CAS  PubMed  Google Scholar 

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Manser, E., Leung, T., Salihuddin, H. et al. A brain serine/threonine protein kinase activated by Cdc42 and Rac1. Nature 367, 40–46 (1994). https://doi.org/10.1038/367040a0

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