Separate Signals in Blood Cell Development

Science's STKE  21 Oct 2003:
Vol. 2003, Issue 205, pp. tw411-TW411
DOI: 10.1126/stke.2003.205.tw411

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]