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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
Abstract:
The Rho guanosine triphosphatases (GTPases) Rac1 and Rac2 arecritical signaling regulators in mammalian cells. The deletionof both Rac1 and Rac2 murine alleles leads to a massive egressof hematopoietic stem/progenitor cells (HSC/Ps) into the bloodfrom the marrow, whereas Rac1–/– but not Rac2–/–HSC/Ps fail to engraft in the bone marrow of irradiated recipientmice. In contrast, Rac2, but not Rac1, regulates superoxideproduction and directed migration in neutrophils, and in eachcell type, the two GTPases play distinct roles in actin organization,cell survival, and proliferation. Thus, Rac1 and Rac2 regulateunique 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.
To whom correspondence should be addressed. E-mail: david.williams{at}chmcc.org
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Blood
107, 2968-2975
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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.
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
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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
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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 »
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
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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
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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 »
Actin Depolymerization Transduces the Strength of B-Cell Receptor Stimulation.
Rac2 Regulates Neutrophil Chemotaxis, Superoxide Production, and Myeloid Colony Formation through Multiple Distinct Effector Pathways.
D. Carstanjen, A. Yamauchi, A. Koornneef, H. Zang, M.-D. Filippi, C. Harris, J. Towe, S. Atkinson, Y. Zheng, M. C. Dinauer, et al. (2005)
J. Immunol.
174, 4613-4620
|Abstract »|Full Text »|PDF »
Protein O-GlcNAc Modulates Motility-associated Signaling Intermediates in Neutrophils.
Control of neutrophil pseudopods by fluid shear: role of Rho family GTPases.
A. Makino, M. Glogauer, G. M. Bokoch, S. Chien, and G. W. Schmid-Schonbein (2005)
Am J Physiol Cell Physiol
288, C863-C871
|Abstract »|Full Text »|PDF »
A STAT5 modifier locus on murine chromosome 7 modulates engraftment of hematopoietic stem cells during steady-state hematopoiesis.
RhoH, a hematopoietic-specific Rho GTPase, regulates proliferation, survival, migration, and engraftment of hematopoietic progenitor cells.
Y. Gu, A. C. Jasti, M. Jansen, and J. E. Siefring (2005)
Blood
105, 1467-1475
|Abstract »|Full Text »|PDF »
Rac GTPase Isoform-specific Regulation of NADPH Oxidase and Chemotaxis in Murine Neutrophils in Vivo: ROLE OF THE C-TERMINAL POLYBASIC DOMAIN.
A. Yamauchi, C. C. Marchal, J. Molitoris, N. Pech, U. Knaus, J. Towe, S. J. Atkinson, and M. C. Dinauer (2005)
J. Biol. Chem.
280, 953-964
|Abstract »|Full Text »|PDF »
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