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Rho GTPases and Regulation of Hematopoietic Stem Cell Localization
Abstract
Bone marrow engraftment in the context of hematopoietic stem cell and progenitor (HSC/P) transplantation is based on the ability of intravenously administered cells to lodge in the medullary cavity and be retained in the appropriate marrow space, a process referred to as homing. It is likely that homing is a multistep process, encompassing a sequence of highly regulated events that mimic the migration of leukocytes to inflammatory sites. In leukocyte biology, this process includes an initial phase of tethering and rolling of cells to the endothelium via E- and P-selectins, firm adhesion to the vessel wall via integrins that appear to be activated in an "inside-out" fashion, transendothelial migration, and chemotaxis through the extracellular matrix (ECM) to the inflammatory nidus. For HSC/P, the cells appear to migrate to the endosteal space of the bone marrow. A second phase of engraftment involves the subsequent interaction of specific HSC/P surface receptors, such as alpha(4)beta(1) integrin receptors with vascular cell-cell adhesion molecule-1 and fibronectin in the ECM, and interactions with growth factors that are soluble, membrane, or matrix bound. We have utilized knockout and conditional knockout mouse lines generated by gene targeting to study the role of Rac1 and Rac2 in blood cell development and function. We have determined that Rac is activated via stimulation of CXCR4 by SDF-1, by adhesion via beta(1) integrins, and via stimulation of c-kit by the stem cell fac…
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“Rac2 is predominantly expressed in hematopoietic cells, whereas Rac1 is ubiquitously expressed (16).”
From Pak and Rac GTPases promote oncogenic KIT–induced neoplasms (2013) · cites this paper as [16]
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Metadata
- Venue
- Methods in Enzymology
- Publisher
- Elsevier
- Published
- 2008
- Pages
- 365-393
- ISSN
- 0076-6879
- Cited by
- 54
- References
- 9
- Language
- en
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