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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{dagger}

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.

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

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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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