GTPASES Separate Signals in Blood Cell Development

Guanosine triphosphatases (GTPases) of the Ras superfamily regulate broad cellular functions, including activity of the cytoskeleton, apoptosis, gene transcription, and intracellular trafficking. The Rho subfamily GTPases, Rac-1 and Rac-2, have been implicated in several of these activities within hematopoietic stem cell and leukocytes. Using conditional deletion of the Rac-1 and Rac-2 genes, Gu et al. determined that although both proteins are required to regulate actin assembly, Rac-1 specifically controls stem cell proliferation with Rac-2 governing cellular migration and production of the superoxide burst in neutrophils. In B cells, Walmsley et al. observed vital cooperation between the two GTPases, with deletion of both alleles resulting in a block in B cell development. This finding corresponded with a signaling defect and failure to express the receptor for the Baff protein, a critical regulator of B cell function and development.

Y. Gu, M.-D. Filippi, J. A. Cancelas, J. E. Siefring, E. P. Williams, A. C. Jasti, C. E. Harris, A. W. Lee, R. Prabhakar, S. J. Atkinson, D. J. Kwiatkowski, D. A. Williams, Hematopoietic cell regulation by Rac1 and Rac2 guanosine triphosphatases. Science 302, 445-449 (2003). [Abstract] [Full Text]

M. J. Walmsley, S. K. T. Ooi, L. F. Reynolds, S. Harless Smith, S. Ruf, A. Mathiot, L. Vanes, D. A. Williams, M. P. Cancro, V. L. J. Tybulewicz, Critical roles for Rac1 and Rac2 GTPases in B cell development and signaling. Science 302, 459-462 (2003). [Abstract] [Full Text]

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REPORTS
Hematopoietic Cell Regulation by Rac1 and Rac2 Guanosine Triphosphatases

Yi Gu, Marie-Dominique Filippi, Jose A. Cancelas, Jamie E. Siefring, Emily P. Williams, Aparna C. Jasti, Chad E. Harris, Andrew W. Lee, Rethinasamy Prabhakar, Simon J. Atkinson, David J. Kwiatkowski, and David A. Williams (17 October 2003)
Science 302 (5644), 445. [DOI: 10.1126/science.1088485]
 |  Abstract »  |  Full Text »  |  PDF »  |  Supporting Online Material »

REPORTS
Critical Roles for Rac1 and Rac2 GTPases in B Cell Development and Signaling

Marita J. Walmsley, Steen K. T. Ooi, Lucinda F. Reynolds, Susan Harless Smith, Sandra Ruf, Anne Mathiot, Lesley Vanes, David A. Williams, Michael P. Cancro, and Victor L. J. Tybulewicz (17 October 2003)
Science 302 (5644), 459. [DOI: 10.1126/science.1089709]
 |  Abstract »  |  Full Text »  |  PDF »  |  Supporting Online Material »