A role for Rac in Tiaml-induced membrane ruffling and invasion (original) (raw)

Nature volume 375, pages 338–340 (1995)Cite this article

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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Author notes

  1. John G. Collard: To whom correspondence should be addressed.

Authors and Affiliations

  1. Division of Cell Biology, The Netherlands Cancer Institute, 121 Plesmanlaan, 1066 CX, Amsterdam, The Netherlands
    Frits Michiels, Gaston G. M. Habets, Jord C. Stam, Rob A. van der Kammen & John G. Collard

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  1. Frits Michiels
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  2. Gaston G. M. Habets
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  3. Jord C. Stam
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  4. Rob A. van der Kammen
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  5. John G. Collard
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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). https://doi.org/10.1038/375338a0

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