TY  - JOUR
A1  - Schwarz, Kerstin
A1  - Aschenbrenner, Frank
A1  - Rüster, Brigitte Inge
A1  - Kampfmann, Manuela
A1  - Komor, Martina
A1  - Hofmann, Wolf-Karsten
A1  - Ruthardt, Martin
A1  - Henschler, Reinhard
A1  - Bug, Gesine
T1  - Novel role of Ras-GTPase Activating Protein SH3 Domain-Binding Protein G3BP in adhesion and migration of 32D myeloid progenitor cells
T2  - The open hematology journal
N2  - 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.
KW  - G3BP
KW  - Rho GTPases
KW  - 32D progenitor cells
KW  - adhesion
KW  - migration
KW  - homing
KW  - toxin B
KW  - lethal toxin
Y1  - 2012
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/28711
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-287118
SN  - 1874-2769
N1  - © Schwarz et al.; Licensee Bentham Open. This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
VL  - 6
IS  - 6
SP  - 1
EP  - 7
PB  - Bentham Open
CY  - Sharjah
ER  -