A role for Rac in Tiaml-induced membrane ruffling and invasion

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Abstract

RHO-LIKE GTPases have been implicated in the regulation of the actin cytoskeleton which controls the morphology, adhesion and motility of cells1-3. Like Ras proteins, they become activated when bound GDP is exchanged for GTP, a process catalysed by GDP-dissociation stimulator (GDS) proteins4. Several GDS proteins specific for Rho-like GTPases have been identified5-8. Most of these contain a conserved catalytic domain, the DBL-homology (DH) domain9, and activate Cdc42 or Rho but not Rac5-8. We have isolated the invasion-inducing Tiaml gene, which also encodes a protein with a DH domain10. Here we show that Tiaml is a GDS protein for Rho-like GTPases in vitro. In fibroblasts, Tiaml induces a similar phenotype as constitutively activated (Vll)Racl, including membrane ruffling, and this is inhibited by dominant negative (N17)Racl. Moreover, T-lymphoma cells expressing V12Racl become invasive, indicating that the Tiaml-Rae signalling pathway could be operating in the invasion and metastasis of tumour cells.

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References

  1. 1

    Hall, A. Molec. Biol. Cell 3, 475–479 (1992).

  2. 2

    Tominaga, T. et al. J. Cell Biol. 120, 1529–1537 (1993).

  3. 3

    Takaishi, K. et al. Molec. cell. Biol. 13, 72–79 (1993).

  4. 4

    Boguski, M. S. & McCormick, F. Nature 366, 643–654 (1993).

  5. 5

    Hiraoka, K. et al. Biochem. biophys. Res. Commun. 182, 921–930 (1992).

  6. 6

    Hart, M. J. et al. Nature 354, 311–314 (1991).

  7. 7

    Zheng, Y., Cerione, R. & Bender, A. J. biol. Chem. 269, 2369–2372 (1994).

  8. 8

    Horii, Y. et al. EMBO J. 13, 4776–4786 (1994).

  9. 9

    Hart, M. J. et al. J. biol. Chem. 269, 62–65 (1994).

  10. 10

    Habets, G. G. M. et al. Cell 77, 537–549 (1994).

  11. 11

    Chuang, T. H., Xu, X. M., Quilliam, L. A. & Bokoch, G. M. Biochemical J. 303, 761–767 (1994).

  12. 12

    Shinjo, K. et al. Proc. natn. Acad. Sci. U.S.A. 87, 9853–9857 (1990).

  13. 13

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

  14. 14

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

  15. 15

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

  16. 16

    Nishiyama, T. et al. Molec. cell. Biol. 14, 2447–2456 (1994).

  17. 17

    Nobes, C. & Hall, A. Curr. Opin. Genet. Dev. 4, 77–81 (1994).

  18. 18

    Cook, S. & McCormick, F. Nature 369, 361–362 (1994).

  19. 19

    Habets, G. G. M., van der Kammen, R. A., Stam, J. C., Michiels, F. & Collard, J. G. Oncogene 10, 1371–1376 (1995).

  20. 20

    Bokoch, G. M. Curr. Opin. Cell Biol. 6, 212–218 (1994).

  21. 21

    Qiu, R-G., Chen, J., Kirn, D., McCormick, F. & Symons, M. Nature 374, 457–459 (1995).

  22. 22

    Evan, G. I. et al. Molec. cell. Biol. 5, 3610–3616 (1985).

  23. 23

    Smith, D. B. & Johnson, K. S. Gene 67, 31–40 (1988).

  24. 24

    Collard, J. G., Schijven, J. F. & Roos, E. Cancer Res. 47, 754–759 (1987).

  25. 25

    Dranoff, G. et al. Proc. natn. Acad. Sci. U.S.A. 90, 3539–3543 (1993).

  26. 26

    Pear, W. S. et al. Proc. natn. Acad. Sci. U.S.A. 90, 8392–8396 (1993).

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Michiels, F., Habets, G., Stam, J. et al. A role for Rac in Tiaml-induced membrane ruffling and invasion. Nature 375, 338–340 (1995) doi:10.1038/375338a0

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