Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

The GTPase superfamily: a conserved switch for diverse cell functions

Nature volume 348, pages 125–132 (1990)Cite this article

Abstract

Proteins that bind and hydrolyse GTP are being discovered at a rapidly increasing rate. Each of these many GTPases acts as a molecular switch whose 'on' and 'off states are triggered by binding and hydrolysis of GTP. Conserved structure and mechanism in myriad versions of the switch—in bacteria, yeast, flies and vertebrates—suggest that all derive from a single primordial protein, repeatedly modified in the course of evolution to perform a dazzling variety of functions.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

References

  1. Jurnak, F. Science 230, 32–36 (1985).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  2. La Cour, T. F. M., Nyborg, J., Thirup, S. & Clark, B. F. C. EMBO J. 4, 2385–2388 (1985).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. de Vois, A. M. et al. Science 239, 888–893 (1988).

    ADS  Google Scholar 

  4. Pai, E. F. et al. Nature 341, 209–214 (1989).

    ADS  CAS  Google Scholar 

  5. Milburn, M. V. et al. Science 247, 939–945 (1990).

    ADS  CAS  Google Scholar 

  6. Brünger, A. T. et al. Proc. natn. Acad. Sci. U.S.A. 87, 4849–4853 (1990).

    ADS  Google Scholar 

  7. Kaziro, Y. Biochim. biophys. Acta 505, 95–127 (1978).

    CAS  Google Scholar 

  8. Thompson, R. C. Trends biochem. Sci. 13, 91–93 (1988).

    CAS  Google Scholar 

  9. Neer, E. J. & Clapham, D. E. Nature 333, 129–134 (1988).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  10. Stryer, L. & Bourne, H. R. Rev. cell. Biol. 2, 391–419 (1986).

    CAS  Google Scholar 

  11. Birnbaumer, L. et al. Kidney Internat. (Suppl.) 32, S14–S37 (1987).

    Google Scholar 

  12. Freissmuth, M., Caset, P. J. & Gilman, A. G. FASEB J. 3, 2125–2131 (1989).

    CAS  Google Scholar 

  13. Ross, E. M. Neuron 3, 141–152 (1989).

    CAS  PubMed  Google Scholar 

  14. Romisch, K. et al. Nature 340, 478–482 (1989).

    ADS  CAS  PubMed  Google Scholar 

  15. Bernstein, H. D. et al. Nature 340, 482–486 (1989).

    ADS  CAS  PubMed  Google Scholar 

  16. Hann, B. C., Poritz, M. A. & Walter, P. J. Cell Biol. 109, 3223–3230 (1989).

    CAS  PubMed  Google Scholar 

  17. Lauffer, L. et al. Nature 318, 334–338 (1985).

    ADS  CAS  PubMed  Google Scholar 

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

    CAS  Google Scholar 

  19. McCormick, F. Cell 56, 5–8 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Salminen, A. & Novick, P. J. Cell 49, 527–538 (1987).

    CAS  PubMed  Google Scholar 

  21. Bacon, R. A., Salminen, A., Ruohola, H., Novick, P. & Ferro-Novick, S. J. Cell Biol. 109, 105–1022 (1989).

    Google Scholar 

  22. Schmitt, H. D., Wagner, P., Pfaff, E. & Gallwitz, D. Cell 47, 401–412 (1986).

    CAS  PubMed  Google Scholar 

  23. Segev, N., Mulholland, J. & Botstein, D. Cell 52, 915–924 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Bourne, H. R. Cell 53, 669–671 (1988).

    CAS  Google Scholar 

  25. Masters, S. B., Stroud, R. M. & Bourne, H. R. Protein Engng 1, 47–54 (1986).

    CAS  Google Scholar 

  26. Heidman, W. & Bourne, H. R. in G Proteins (eds Birnbaumer, L. & lyengar, R.) 17–40 (Academic, San Diego, 1990).

    Google Scholar 

  27. Gibbs, J. B. et al. in ADP-ribosylating Toxins and G Proteins. Insights into Signal Transduction (eds Moss, J. & Vaughan, M.) 381–396 (American Society for Microbiology, Washington DC, 1990).

    Google Scholar 

  28. Price, S. R., Barber, A. & Moss, J. in ADP-ribosylating Toxins and G Proteins. Insights into Signal Transduction (eds Moss, J. & Vaughan, M.) 397–424 (American Society for Microbiology Washington DC, 1990).

    Google Scholar 

  29. Trahey, M. & McCormick, F. Science 238, 542–545 (1987).

    ADS  CAS  Google Scholar 

  30. Gilman, A. G. A. Rev. Biochem. 56, 615–649 (1987).

    CAS  Google Scholar 

  31. Thompson, R. C., Dix, D. B. & Karim, A. M. J. biol. Chem. 261, 4868–4874 (1986).

    CAS  Google Scholar 

  32. Fong, H. K. W., Yoshimoto, K. K., Eversole-Cire, P. & Simon, M. I. Proc. natn. Acad. Sci. U.S.A. 85, 3066–3070 (1988).

    ADS  CAS  Google Scholar 

  33. Matsuoka, M., Itoh, H. Kozasa, T. & Kaziro, Y. Proc. natn. Acad. Sci. U.S.A. 85, 5384–5388 (1988).

    ADS  CAS  Google Scholar 

  34. Strathmann, M., Wilkie, T. M. & Simon, M. I. Proc. natn. Acad. Sci. U.S.A. 86, 7407–7409 (1989).

    ADS  CAS  Google Scholar 

  35. Bourne, H. R. Cold Spring Harbor Symp. quant. Biol. 53, 1019–1031 (1988).

    CAS  PubMed  Google Scholar 

  36. Bourne, H. R. & DeFranco, A. L. In Oncogenes and the Molecular Origins of Cancer (ed. Weinberg, R.) 97–124 (Cold Spring Harbor Laboratory, New York, 1989).

    Google Scholar 

  37. Stryer, L. A. Rev. Neurosci. 9, 87–119 (1986).

    CAS  Google Scholar 

  38. Casey, P. J. & Gilman, A. G. J. biol. Chem. 263, 2577–2580 (1988).

    CAS  Google Scholar 

  39. Graziano, M. & Gilman, A. G. J. biol. Chem. 264, 15475–15482 (1989).

    CAS  PubMed  Google Scholar 

  40. Landis, C. A. et al. Nature 340, 692–696 (1989).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  41. Dietzel, C. & Kurjan, J. Cell 50, 1001–1010 (1987).

    CAS  Google Scholar 

  42. Nakafuku, M., Itoh, H., Nakamura, S. & Kaziro, Y. Proc. natn. Acad. Sci. U.S.A. 84, 2140–2144 (1987).

    ADS  CAS  Google Scholar 

  43. Miyajima, I. et al. Cell 50, 1011–1019 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Whiteway, M. et al. Cell 56, 457–477 (1989).

    Google Scholar 

  45. Bourne, H. R., Coffino, P. & Tomkins, G. M. Science 187, 750–752 (1975).

    ADS  CAS  PubMed  Google Scholar 

  46. Harris, B. A., Robishaw, J. D., Mumby, S. M. & Gilman, A. G. Science 229, 1274–1277 (1985).

    ADS  CAS  PubMed  Google Scholar 

  47. Robinshaw, J. D., Russell, D. W., Harris, B. A., Smigel, M. D. & Gilman, A. G. Proc. natn. Acad. Sci. U.S.A. 83, 1251–1255 (1986).

    ADS  Google Scholar 

  48. Miyajima, I., Arai, K. I. & Matsumoto, K. Molec. cell. Biol. 9, 2289–2297 (1989).

    CAS  PubMed  Google Scholar 

  49. Bourne, H. R. Nature 337, 504–505 (1989).

    ADS  CAS  PubMed  Google Scholar 

  50. Birchmeier, C., Broek, D. & Wigler, M. Cell 43, 615–621 (1985).

    CAS  Google Scholar 

  51. Bar-Sagi, D. & Feramisco, J. R. Cell 42, 841–848 (1985).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Satoh, T., Nakamura, S. & Kaziro, Y. Molec. cell. Biol. 7, 4553–4556 (1987).

    CAS  Google Scholar 

  53. John, J., Frech, M. & Wittinghofer, A. J. biol. Chem. 263, 11792–11799 (1988).

    CAS  PubMed  Google Scholar 

  54. Neal, S. E., Eccleston, J. F., Hall, A. & Webb, M. R. J. biol. Chem. 263, 19718–19722 (1988).

    CAS  Google Scholar 

  55. West, M., Kung, H.-F. & Kamata, T. FEBS Lett. 259, 245–248 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Wolfman, A. & Macara, I. G. Science 248, 67–69 (1990).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  57. Downward, J., Riehl, R., Wu, L. & Weinberg, R. A. Proc. natn. Acad. Sci. U.S.A. 87, 5998–6002 (1990).

    ADS  CAS  Google Scholar 

  58. Vogel, U.S. et al. Nature 335, 90–93 (1988).

    ADS  CAS  Google Scholar 

  59. Trahey, M. et al. Science 242, 1697–1700 (1988).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  60. Tabaka, K. et al. Cell 60, 803–807 (1990).

    Google Scholar 

  61. Sigal, I. S. et al. Proc. natn. Acad. Sci. U.S.A. 83, 952–956 (1986).

    ADS  CAS  Google Scholar 

  62. Walter, M., Clark, S. G. & Levinson, A. D. Science 233, 649–652 (1986).

    ADS  CAS  PubMed  Google Scholar 

  63. Feig, L. A. & Cooper, G. M. Molec. cell. Biol. 8, 2472–2478 (1988).

    CAS  PubMed  Google Scholar 

  64. Ballester, R. et al. Cell 59, 681–686 (1989).

    CAS  Google Scholar 

  65. Zhang, K. et al. Nature 346, 719–723 (1990).

    Google Scholar 

  66. Downward, J., Graves, J. D., Warne, P. H., Rayter, S. & Cantrell, D. A. Nature 346, 719–723 (1990).

    ADS  CAS  Google Scholar 

  67. Gibbs, J. B., Schaber, M. D., Schofield, T. L., Scolnick, E. M. & Sigal, I. S. Proc. natn. Acad. Sci. U.S.A. 86, 6630–6634 (1989).

    ADS  CAS  Google Scholar 

  68. Gibbs, J. B. & Marshall, M. S. Microbiol. Rev. 53, 171–185 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Hall, A. Cell 61, 921–923 (1990).

    CAS  PubMed  Google Scholar 

  70. Yatani, A., Okabe, K., Polakis, P., McCormick, F. & Brown, A. M. Cell 61, 769–776 (1990).

    CAS  Google Scholar 

  71. Field, J., Broek, D., Kataoka, T. & Wigler, M. Molec. cell. Biol. 7, 2128–2183 (1987).

    CAS  Google Scholar 

  72. Broek, D. et al. Cell 41, 763–769 (1985).

    CAS  PubMed  Google Scholar 

  73. Wigler, M. et al. Cold Spring Harbor Symp. quant. Biol. 53, 649–655 (1988).

    CAS  PubMed  Google Scholar 

  74. Toda, T., Cameron, S., Sass, P., Zoller, M. & Wigler, M. Cell 50, 277–287 (1987).

    CAS  PubMed  Google Scholar 

  75. Camonis, J. H. et al. EMBO J. 5, 375–380 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Broek, D. et al. Cell 48, 789–799 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Powers, S., O'Neill, K. & Wigler, M. Molec. cell. Biol. 9, 390–395 (1989).

    CAS  Google Scholar 

  78. Créchet, J.-B. et al. Science 248, 866–868 (1990).

    ADS  PubMed  Google Scholar 

  79. Ellis, C., Moran, M., McCormick, F. & Pawson, T. Nature 343, 377–381 (1990).

    ADS  CAS  Google Scholar 

  80. Molloy, C. J. et al. Nature 342, 711–714 (1989).

    ADS  CAS  Google Scholar 

  81. Kaplan, D. R., Morrison, D. K., Wong, G., McCormick, F. & Williams, L. T. Cell 61, 125–133 (1990).

    CAS  PubMed  Google Scholar 

  82. Kazlauskas, A., Ellis, C., Pawson, T. & Cooper, J. A. Science 247, 1578–1581 (1990).

    ADS  CAS  PubMed  Google Scholar 

  83. Xu, G. et al. Cell 62, 599–608 (1990).

    CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  85. Frech, M. et al. Science 249, 169–171 (1990).

    ADS  CAS  PubMed  Google Scholar 

  86. Hata, Y. et al. J. biol. Chem. 265, 7104–7107 (1990).

    CAS  PubMed  Google Scholar 

  87. Kikuchi, A., Sasaki, T., Araki, S., Hata, Y. & Takai, Y. J. biol. Chem. 264, 9133–9136 (1989).

    CAS  PubMed  Google Scholar 

  88. Kitayama, H., Sugimoto, Y., Matsuzaki, T., Ikawa, Y. & Noda, M. Cell 56, 77–84 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Sasaki, T. et al. J. biol. Chem. 265, 2333–2337 (1990).

    CAS  PubMed  Google Scholar 

  90. Ueda, T., Kikuchi, A., Ohga, N., Yamamoto, J. & Takai, Y. J. biol. Chem. 265, 9373–9380 (1990).

    CAS  PubMed  Google Scholar 

  91. Matsui, Y. et al. Molec. cell. Biol. 10, 4116–4122 (1990).

    CAS  PubMed  Google Scholar 

  92. Araki, S., Kikuchi, A., Hata, Y., Isomura, M. & Takai, Y. J. biol. Chem. 265, 13007–13015 (1990).

    CAS  PubMed  Google Scholar 

  93. Gutierrez, L., Magee, A. I., Marshall, C. J. & Hancock, J. F. EMBO J. 8, 1093–1098 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Hancock, J. F., Magee, A. I., Childs, J. E. & Marshall, C. J. Cell 57, 1167–1177 (1989).

    CAS  Google Scholar 

  95. Clarke, S., Vogel, J. P., Deschenes, R. J. & Stock, J. Proc. natn. Acad. Sci. U.S.A. 85, 4643–4647 (1988).

    ADS  CAS  Google Scholar 

  96. Willumsen, B. M., Christensen, A., Hubbert, N. L., Papageorge, A. G. & Lowy, D. R. Nature 310, 583–586 (1984).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  97. Walworth, N. C., Goud, B., Kabcenell, A. K. & Novick, P. J. EMBO J. 8, 1685–1693 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Molenaar, C. M. T., Prange, R. & Gallwitz, D. EMBO J. 7, 971–976 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Maltese, W. A., Sheridan, K. M., Repko, E. M. & Erdman, R. A. J. biol. Chem. 265, 2148–2155 (1990).

    CAS  PubMed  Google Scholar 

  100. Backlund, P. S. & Aksamit, R. R. J. biol. Chem. 263, 15864–15867 (1988).

    CAS  PubMed  Google Scholar 

  101. Melancon, P. et al. Cell 51, 1053–1062 (1987).

    CAS  Google Scholar 

  102. Mayorga, L. S., Diaz, R. & Stahl, P. D. Science 244, 1475–1477 (1989).

    ADS  CAS  Google Scholar 

  103. Mayorga, L. S., Diaz, R., Colombo, M. I. & Stahl, P. D. Cell Reg. 1, 113–124 (1989).

    CAS  Google Scholar 

  104. Ruohola, H., Kabcenell, A. K. & Ferro-Novick, S. J. Cell Biol. 107, 1465–1476 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Baker, D., Hicke, L., Rexach, M., Schleyer, M. & Schekman, R. Cell 54, (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Schmitt, H. D., Puzicha, M. & Gallwitz, D. Cell 53, 635–647 (1988).

    CAS  PubMed  Google Scholar 

  107. Haubruck, H., Prange, R., Vorgias, C. & Gallwitz, D. EMBO J. 8, 1427–1432 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Goud, B., Salminen, A., Walworth, N. C. & Novick, P. J. Cell 53, 753–768 (1988).

    CAS  Google Scholar 

  109. Salminen, A. & Novick, P. J. J. Cell Biol. 109, 1023–1036 (1989).

    CAS  PubMed  Google Scholar 

  110. Chavrier, P., Parton, R. G., Hauri, H. P., Simons, K. & Zerial, M. Cell 62, 317–329 (1990).

    CAS  PubMed  Google Scholar 

  111. Connolly, T. & Gilmore, R. Cell 57, 599–610 (1989).

    CAS  PubMed  Google Scholar 

  112. Dholakia, J. N. & Wahba, A. J. J. biol. Chem. 264, 546–550 (1989).

    CAS  PubMed  Google Scholar 

  113. Wessling-Resnick, M. & Johnson, G. L. J. biol. Chem. 262, 12444–12447 (1987).

    CAS  PubMed  Google Scholar 

  114. Wessling-Resnick, M. & Johnson, G. L. J. biol. Chem. 262, 3697–3705 (1987).

    CAS  PubMed  Google Scholar 

  115. Hingorani, V. N., Tobias, D. T., Henderson, J. T. & Ho, Y. K. J. biol. Chem. 263, 6916–8926 (1988).

    CAS  PubMed  Google Scholar 

  116. Reed, R. R. Cell 60, 1–2 (1990).

    CAS  PubMed  Google Scholar 

  117. Fischer V. et al. Proc. natn. Acad. Sci. U.S.A. 87, 1988–1992 (1990).

    ADS  Google Scholar 

  118. Kim, S., Kikuchi, A., Mizoguchi, A. & Takai, Y. Molec. Brain Res. 6, 167–176 (1989).

    CAS  PubMed  Google Scholar 

  119. Mizoguchi, A. et al. J. biol. Chem. 265, 11872–11879 (1990).

    CAS  PubMed  Google Scholar 

  120. Darchen, F. et al. Proc. natn. Acad. Sci. U.S.A. 87, 5692–5696 (1990).

    ADS  CAS  Google Scholar 

  121. Sekine, A., Fujiwara, M. & Narumiya, S. J. biol. Chem. 264, 8602–8605 (1989).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  123. Chardin, P. et al. EMBO J. 8, 1087–1092 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Kikuchi, A., Yamamoto, K., Fujita, T. & Takai, Y. J. biol. Chem. 263, 16303–16308 (1988).

    CAS  PubMed  Google Scholar 

  125. Bender, A. & Pringle, J. R. Proc. natn. Acad. Sci. U.S.A. 86, 9976–9980 (1989).

    ADS  CAS  Google Scholar 

  126. Johnson, D. I. & Pringle, J. R. J. Cell Biol. (in the press).

  127. Sewell, J. L. & Kahn, R. A. Proc. natn. Acad. Sci. U.S.A. 85, 4620–4624 (1988).

    ADS  CAS  Google Scholar 

  128. Kahn, R. A. & Gilman, A. G. J. biol. Chem. 261, 7906–7911 (1986).

    CAS  PubMed  Google Scholar 

  129. Sanders, D. A. Cell Growth Diff. 1, 251–258 (1990).

    CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. David A. Sanders

    Present address: the Whitehead Institute for Biomedical Reserach, Cambridge, Massachusetts, 02142, USA

Affiliations

  1. Departments of Pharmacology and Medicine and the Cardiovascular Research Institute, University of California, San Francisco, California, 94143, USA

    Henry R. Bourne

  2. was previously in the Department of Pharmacology and Medicine at the University of California, San Francisco and at the CETUS Corporation

    David A. Sanders

  3. Department of Molecular Biology, CETUS Corporation, Emeryville, California, 94608, USA

    Frank McCormick

Authors
  1. Henry R. Bourne
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David A. Sanders
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Frank McCormick
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Bourne, H., Sanders, D. & McCormick, F. The GTPase superfamily: a conserved switch for diverse cell functions. Nature 348, 125–132 (1990). https://doi.org/10.1038/348125a0

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/348125a0

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing