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Rac GTPases play critical roles in early T-cell development

Dumont, Celine, Corsoni-Tadrzak, Agnieszka, Ruf, Sandra, de Boer, Jasper, Williams, Adam, Turner, Martin, Kioussis, Dimitris, Tybulewicz, Victor L. J.·2009·Blood
DOI 10.1182/blood-2008-09-181180
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Abstract

The Rac1 and Rac2 GTPases play important roles in many processes including cytoskeletal reorganization, proliferation, and survival, and are required for B-cell development. Previous studies had shown that deficiency in Rac2 did not affect T-cell development, whereas the function of Rac1 in this process has not been investigated. We now show that simultaneous absence of both GTPases resulted in a very strong developmental block at the pre-TCR checkpoint and in defective positive selection. Unexpectedly, deficiency of Rac1 and Rac2 also resulted in the aberrant survival of thymocytes lacking expression of TCRβ, showing hallmarks of hyperactive Notch signaling. Furthermore, we found a similar novel phenotype in the absence of Vav1, Vav2, and Vav3, which function as guanine nucleotide exchange factors for Rac1 and Rac2. These results show that a pathway containing Vav and Rac proteins may negatively regulate Notch signaling during early thymic development.

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Cited by

Metadata

Authors
Dumont, C., Corsoni-Tadrzak, A., Ruf, S., de Boer, J., Williams, A., Turner, M., Kioussis, D., & Tybulewicz, V. L. J.
Affiliations
  • Divisions of Immune Cell Biology and
  • Molecular Immunology, Medical Research Council (MRC) National Institute for Medical Research, London; and
  • The Babraham Institute, Cambridge, United Kingdom
Venue
Blood
Publisher
American Society of Hematology
Published
2009-04-23
Volume
113
Issue
17
Pages
3990-3998
ISSN
  • 0006-4971
  • 1528-0020
DOI
10.1182/blood-2008-09-181180
Cited by
66
References
3
Language
en

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