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Article Dans Une Revue Journal of Biological Chemistry Année : 2000

Characterization of TCL, a New GTPase of the Rho Family related to TC10 and Cdc42

Résumé

GTPases of the Rho family control a wide variety of cellular processes such as cell morphology, motility, proliferation, differentiation, and apoptosis. We report here the characterization of a new Rho member, which shares 85% and 78% amino acid similarity to TC10 and Cdc42, respectively. This GTPase, termed as TC10-like (TCL) is encoded by an unexpectedly large locus, made of five exons spanning over 85 kilobases on human chromosome 14. TCL mRNA is 2.5 kilobases long and is mainly expressed in heart. In vitro, TCL shows rapid GDP/GTP exchange and displays higher GTP dissocia-tion and hydolysis rates than TC10. Using the yeast two-hybrid system and GST pull-down assays, we show that GTP-bound but not GDP-bound TCL protein directly interacts with Cdc42/Rac interacting binding domains, such as those found in PAK and WASP. Despite its overall similarity to TC10 and Cdc42, the constitutively active TCL mutant displays distinct morphogenic activity in REF-52 fibroblasts, producing large and dynamic F-actin-rich ruffles on the dorsal cell membrane. Interestingly , TCL morphogenic activity is blocked by dominant negative Rac1 and Cdc42 mutants, suggesting a cross-talk between these three Rho GTPases.
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Dates et versions

hal-02267476 , version 1 (26-06-2020)

Identifiants

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Emmanuel Vignal, Marion de Toledo, Franck Comunale, Angela Ladopoulou, Cécile Gauthier-Rouvière, et al.. Characterization of TCL, a New GTPase of the Rho Family related to TC10 and Cdc42. Journal of Biological Chemistry, 2000, 275 (46), pp.36457-36464. ⟨10.1074/jbc.M003487200⟩. ⟨hal-02267476⟩
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