Differential motility of p190bcr-abl- and p210bcr-abl-expressing cells: respective roles of Vav and Bcr-Abl GEFs - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Oncogene Année : 2008

Differential motility of p190bcr-abl- and p210bcr-abl-expressing cells: respective roles of Vav and Bcr-Abl GEFs

Résumé

The chimeric oncogene Bcr-Abl is known to induce autonomous motility of leukemic cells. We show here that p210(bcr-abl) responsible for chronic myelogenous leukemia induces an amoeboid type of motility while p190(bcr-abl), associated with acute lymphoid leukemia, induces a rolling type of motility. We previously reported that p210(bcr-abl) activates RhoA and Rac1, while p190(bcr-abl) although devoid of a Dbl-homology (DH) domain activates Rac1, but not RhoA. We investigated the regulation of GDP/GTP exchange factor (GEF) activities in the Bcr-Abl complex. For that purpose, different GEF activity mutants of Vav and of Bcr-Abl were constructed and stably transfected in Ba/F3 cells. Using these mutants, we demonstrate that RhoA is exclusively activated by the DH domain of p210(bcr-abl), while Rac1 activation is mostly due to Vav. Inhibition of Rac1 by Vav GEF mutant leads to immobilization of cells. Vav depletion using shRNA also induces immobilization of cells and suppression of GTP-bound Rac1. RhoA inactivation induces the specific loss of amoeboid movements. These results suggest that Rac1 activation by Vav triggers the motility of Bcr-Abl-expressing Ba/F3 cells, while the specific amoeboid mode of motility induced by p210(bcr-abl) is a consequence of RhoA activation.
Fichier principal
Vignette du fichier
Daubon et al, 2007.pdf (660.23 Ko) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-02880258 , version 1 (18-11-2022)

Licence

Paternité

Identifiants

Citer

Thomas Daubon, Jacques Chasseriau, Ayman El Ali, Jacqueline Rivet, Alain Kitzis, et al.. Differential motility of p190bcr-abl- and p210bcr-abl-expressing cells: respective roles of Vav and Bcr-Abl GEFs. Oncogene, 2008, 27 (19), pp.2673-2685. ⟨10.1038/sj.onc.1210933⟩. ⟨hal-02880258⟩
109 Consultations
23 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More