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Rho GTPases are involved in homing and mobilization of hematopoietic stem and progenitor cells due to their
impact on cytoskeleton remodeling. We have previously shown that inhibition of Rho, Rac and Cdc42 clearly impairs adhesion
of normal and leukemic hematopoietic progenitor cells (HPC) to fibronectin and migration in a three-dimensional
stromal cell model. Here, we identified the Ras GTPase-Activating Protein SH3 Domain-Binding Protein (G3BP) as a target
gene of Rho GTPases and analysed its role in regulating HPC motility. Overexpression of G3BP significantly enhanced
adhesion of murine 32D HPC to fibronectin and human umbilical vein endothelial cells, increased the proportion of adherent
cells in a flow chamber assay and promoted cell migration in a transwell assay and a three-dimensional stromal cell model
suggesting a strong impact on the cytoskeleton. Immunofluorescent staining of G3BP-overexpressing fibroblasts revealed a
Rho-like phenotype characterized by formation of actin stress fibers in contrast to the Rac-like phenotype of control fibroblasts.
This is the first report implicating a role for G3BP in Rho GTPase-mediated signalling towards adhesion and migration of
HPC. Our results may be of clinical importance, since G3BP was found overexpressed in human cancers.