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Science 17 October 2003: Vol. 302. no. 5644, pp. 445 - 449 DOI: 10.1126/science.1088485
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Reports
Hematopoietic Cell Regulation by Rac1 and Rac2 Guanosine Triphosphatases
Yi Gu,1*
Marie-Dominique Filippi,1*
Jose A. Cancelas,1,2
Jamie E. Siefring,1
Emily P. Williams,1
Aparna C. Jasti,1
Chad E. Harris,1
Andrew W. Lee,1
Rethinasamy Prabhakar,1
Simon J. Atkinson,3
David J. Kwiatkowski,4
David A. Williams1
The Rho guanosine triphosphatases (GTPases) Rac1 and Rac2 are critical signaling regulators in mammalian cells. The deletion of both Rac1 and Rac2 murine alleles leads to a massive egress of hematopoietic stem/progenitor cells (HSC/Ps) into the blood from the marrow, whereas Rac1/ but not Rac2/ HSC/Ps fail to engraft in the bone marrow of irradiated recipient mice. In contrast, Rac2, but not Rac1, regulates superoxide production and directed migration in neutrophils, and in each cell type, the two GTPases play distinct roles in actin organization, cell survival, and proliferation. Thus, Rac1 and Rac2 regulate unique aspects of hematopoietic development and function.
1 Division of Experimental Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
2 Hoxworth Blood Center, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
3 Department of Medicine, Indiana University, Indianapolis, IN 46202, USA.
4 Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: david.williams{at}chmcc.org
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- Involvement of Phosphoinositide 3-Kinase {gamma}, Rac, and PAK Signaling in Chemokine-induced Macrophage Migration.
- C. Weiss-Haljiti, C. Pasquali, H. Ji, C. Gillieron, C. Chabert, M.-L. Curchod, E. Hirsch, A. J. Ridley, R. H. van Huijsduijnen, M. Camps, et al. (2004)
J. Biol. Chem.
279, 43273-43284
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- Structure and regulation of the neutrophil respiratory burst oxidase: comparison with nonphagocyte oxidases.
- M. T. Quinn and K. A. Gauss (2004)
J. Leukoc. Biol.
76, 760-781
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- The Effect of Anionic Amphiphiles on the Recruitment of Rac in Neutrophils.
- K. Nigorikawa, N. Okamura, and O. Hazeki (2004)
J. Biochem.
136, 463-470
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- Cdc42, Rac1, and Rac2 Display Distinct Patterns of Activation during Phagocytosis.
- A. D. Hoppe and J. A. Swanson (2004)
Mol. Biol. Cell
15, 3509-3519
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- Rac2 is critical for neutrophil primary granule exocytosis.
- D. Abdel-Latif, M. Steward, D. L. Macdonald, G. A. Francis, M. C. Dinauer, and P. Lacy (2004)
Blood
104, 832-839
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- Rho Is Involved in Superoxide Formation during Phagocytosis of Opsonized Zymosans.
- J.-S. Kim, B. A. Diebold, J.-I. Kim, J. Kim, J.-Y. Lee, and J.-B. Park (2004)
J. Biol. Chem.
279, 21589-21597
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- Differential gene expression of human stem progenitor cells derived from early stages of in utero human hematopoiesis.
- F. Shojaei, L. Gallacher, and M. Bhatia (2004)
Blood
103, 2530-2540
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- Rho-family GTPases: it's not only Rac and Rho (and I like it).
- K. Wennerberg and C. J. Der (2004)
J. Cell Sci.
117, 1301-1312
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- Myosin light chain 1 atrial isoform (MLC1A) is expressed in pre-B cells under control of the BOB.1/OBF.1 coactivator.
- H. Laumen, C. Brunner, A. Greiner, and T. Wirth (2004)
Nucleic Acids Res.
32, 1577-1583
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- Current mechanistic scenarios in hematopoietic stem/progenitor cell mobilization.
- T. Papayannopoulou (2004)
Blood
103, 1580-1585
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