Novel Role of Ras-GTPase Activating Protein SH3 Domain-Binding ProteinG3BP in Adhesion and Migration of 32D Myeloid Progenitor Cells

摘要

Rho GTPases are involved in homing and mobilization of hematopoietic stem and progenitor cells due to theirimpact on cytoskeleton remodeling. We have previously shown that inhibition of Rho, Rac and Cdc42 clearly impairs adhesionof normal and leukemic hematopoietic progenitor cells (HPC) to fibronectin and migration in a three-dimensionalstromal cell model. Here, we identified the Ras GTPase-Activating Protein SH3 Domain-Binding Protein (G3BP) as a targetgene of Rho GTPases and analysed its role in regulating HPC motility. Overexpression of G3BP significantly enhancedadhesion of murine 32D HPC to fibronectin and human umbilical vein endothelial cells, increased the proportion of adherentcells in a flow chamber assay and promoted cell migration in a transwell assay and a three-dimensional stromal cell modelsuggesting a strong impact on the cytoskeleton. Immunofluorescent staining of G3BP-overexpressing fibroblasts revealed aRho-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 ofHPC. Our results may be of clinical importance, since G3BP was found overexpressed in human cancers.