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Rho-Like GTPases have been implicated in the regulation of the actin cytoskeleton which controls the morphology, adhesion and motility of cells [1-3]. Like Ras proteins, they become activated when bound GDP is exchanged for GTP, a process catalysed by GDP-dissociation stimulator (GDS) proteins [4]. Several GDS proteins specific for Rho-like GTPases have been identified [5-8]. Most of these contain a conserved catalytic domain, the DBL-homology (DH) domain [9], and activate Cdc42 of Rho but not Rac [5-8]. We have isolated the invasion-inducing Tiam1 gene, which also encodes a protein with a DH domain [10]. Here we show that Tiam1 is a GDS protein for Rho-like GTPases in vitro. In fibroblasts, Tiam1 induces a similar phenotype as constitutively activated (V12)Rac1, including membrane ruffling, and this is inhibited by dominant negative (N17)Rac1. Moreover, T-lymphoma cells expressing V12Rac1 become invasive, indicating that the Tiam1-Rac signalling pathway could be operating in the invasion and metastasis of tumour cells.

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