Novel role of Ras-GTPase Activating Protein SH3 Domain-Binding Protein G3BP in adhesion and migration of 32D myeloid progenitor cells
- 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.
Verfasserangaben: | Kerstin Schwarz, Frank Aschenbrenner, Brigitte Inge Rüster, Manuela Kampfmann, Martina Komor, Wolf-Karsten Hofmann, Martin RuthardtORCiD, Reinhard HenschlerGND, Gesine BugORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-287118 |
DOI: | https://doi.org/10.2174/1874276901206010001 |
ISSN: | 1874-2769 |
Titel des übergeordneten Werkes (Englisch): | The open hematology journal |
Verlag: | Bentham Open |
Verlagsort: | Sharjah |
Dokumentart: | Wissenschaftlicher Artikel |
Sprache: | Englisch |
Datum der Veröffentlichung (online): | 12.02.2013 |
Datum der Erstveröffentlichung: | 23.02.2012 |
Veröffentlichende Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Datum der Freischaltung: | 12.02.2013 |
Freies Schlagwort / Tag: | 32D progenitor cells; G3BP; Rho GTPases; adhesion; homing; lethal toxin; migration; toxin B |
Jahrgang: | 6 |
Ausgabe / Heft: | 6 |
Seitenzahl: | 7 |
Erste Seite: | 1 |
Letzte Seite: | 7 |
Bemerkung: | © 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. |
HeBIS-PPN: | 33146201X |
Institute: | Medizin / Medizin |
DDC-Klassifikation: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Lizenz (Deutsch): | Creative Commons - Namensnennung-Nicht kommerziell 3.0 |