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Science 302 (5644): 445-449

Copyright © 2003 by the American Association for the Advancement of Science

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{dagger}

Abstract: 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.

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* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: david.williams{at}

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J. Biol. Chem. 281, 18652-18659
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RhoG Regulates the Neutrophil NADPH Oxidase.
A. M. Condliffe, L. M. C. Webb, G. J. Ferguson, K. Davidson, M. Turner, E. Vigorito, M. Manifava, E. R. Chilvers, L. R. Stephens, and P. T. Hawkins (2006)
J. Immunol. 176, 5314-5320
   Abstract »    Full Text »    PDF »
Rac1-null Mouse Embryonic Fibroblasts Are Motile and Respond to Platelet-derived Growth Factor.
L. Vidali, F. Chen, G. Cicchetti, Y. Ohta, and D. J. Kwiatkowski (2006)
Mol. Biol. Cell 17, 2377-2390
   Abstract »    Full Text »    PDF »
Enhanced engraftment of hematopoietic stem/progenitor cells by the transient inhibition of an adaptor protein, Lnk.
H. Takizawa, C. Kubo-Akashi, I. Nobuhisa, S.-M. Kwon, M. Iseki, T. Taga, K. Takatsu, and S. Takaki (2006)
Blood 107, 2968-2975
   Abstract »    Full Text »    PDF »
Lack of {alpha}4 integrin expression in stem cells restricts competitive function and self-renewal activity.
G. V. Priestley, L. M. Scott, T. Ulyanova, and T. Papayannopoulou (2006)
Blood 107, 2959-2967
   Abstract »    Full Text »    PDF »
Regulation of NADPH Oxidases: The Role of Rac Proteins.
P. L. Hordijk (2006)
Circ. Res. 98, 453-462
   Abstract »    Full Text »    PDF »
cAMP-induced PKC{zeta} activation increases functional CXCR4 expression on human CD34+ hematopoietic progenitors.
P. Goichberg, A. Kalinkovich, N. Borodovsky, M. Tesio, I. Petit, A. Nagler, I. Hardan, and T. Lapidot (2006)
Blood 107, 870-879
   Abstract »    Full Text »    PDF »
Genetic deletion of Cdc42GAP reveals a role of Cdc42 in erythropoiesis and hematopoietic stem/progenitor cell survival, adhesion, and engraftment.
L. Wang, L. Yang, M.-D. Filippi, D. A. Williams, and Y. Zheng (2006)
Blood 107, 98-105
   Abstract »    Full Text »    PDF »
Isozyme-specific Stimulation of Phospholipase C-{gamma}2 by Rac GTPases.
T. Piechulek, T. Rehlen, C. Walliser, P. Vatter, B. Moepps, and P. Gierschik (2005)
J. Biol. Chem. 280, 38923-38931
   Abstract »    Full Text »    PDF »
Rac1 Is Essential for Platelet Lamellipodia Formation and Aggregate Stability under Flow.
O. J. T. McCarty, M. K. Larson, J. M. Auger, N. Kalia, B. T. Atkinson, A. C. Pearce, S. Ruf, R. B. Henderson, V. L. J. Tybulewicz, L. M. Machesky, et al. (2005)
J. Biol. Chem. 280, 39474-39484
   Abstract »    Full Text »    PDF »
How do stem cells find their way home?.
T. Lapidot, A. Dar, and O. Kollet (2005)
Blood 106, 1901-1910
   Abstract »    Full Text »    PDF »
Isoform-Specific Membrane Targeting Mechanism of Rac during Fc{gamma}R-Mediated Phagocytosis: Positive Charge-Dependent and Independent Targeting Mechanism of Rac to the Phagosome.
T. Ueyama, M. Eto, K. Kami, T. Tatsuno, T. Kobayashi, Y. Shirai, M. R. Lennartz, R. Takeya, H. Sumimoto, and N. Saito (2005)
J. Immunol. 175, 2381-2390
   Abstract »    Full Text »    PDF »
Stem Cell Depletion Through Epidermal Deletion of Rac1.
S. A. Benitah, M. Frye, M. Glogauer, and F. M. Watt (2005)
Science 309, 933-935
   Abstract »    Full Text »    PDF »
Repression of c-Kit and Its Downstream Substrates by GATA-1 Inhibits Cell Proliferation during Erythroid Maturation.
V. Munugalavadla, L. C. Dore, B. L. Tan, L. Hong, M. Vishnu, M. J. Weiss, and R. Kapur (2005)
Mol. Cell. Biol. 25, 6747-6759
   Abstract »    Full Text »    PDF »
CXCL9 inhibits eosinophil responses by a CCR3- and Rac2-dependent mechanism.
P. C. Fulkerson, H. Zhu, D. A. Williams, N. Zimmermann, and M. E. Rothenberg (2005)
Blood 106, 436-443
   Abstract »    Full Text »    PDF »
Generation and Characterization of Rac3 Knockout Mice.
S. Corbetta, S. Gualdoni, C. Albertinazzi, S. Paris, L. Croci, G. G. Consalez, and I. de Curtis (2005)
Mol. Cell. Biol. 25, 5763-5776
   Abstract »    Full Text »    PDF »
Generation of rac3 Null Mutant Mice: Role of Rac3 in Bcr/Abl-Caused Lymphoblastic Leukemia.
Y. J. Cho, B. Zhang, V. Kaartinen, L. Haataja, I. de Curtis, J. Groffen, and N. Heisterkamp (2005)
Mol. Cell. Biol. 25, 5777-5785
   Abstract »    Full Text »    PDF »
Vav1 and Rac Control Chemokine-promoted T Lymphocyte Adhesion Mediated by the Integrin {alpha}4{beta}1.
D. Garcia-Bernal, N. Wright, E. Sotillo-Mallo, C. Nombela-Arrieta, J. V. Stein, X. R. Bustelo, and J. Teixido (2005)
Mol. Biol. Cell 16, 3223-3235
   Abstract »    Full Text »    PDF »

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