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Blood, 23 April 2009, Vol. 113, No. 17, pp. 3990-3998. Prepublished online as a Blood First Edition Paper on December 16, 2008; DOI 10.1182/blood-2008-09-181180. This Article Full Text (PDF) All Versions of this Article: blood-2008-09-181180v1 113/17/3990    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dumont, C. Articles by Tybulewicz, V. L.J. Search for Related Content PubMed PubMed Citation Articles by Dumont, C. Articles by Tybulewicz, V. L.J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 26, 2008 Accepted December 14, 2008 Rac GTPases play critical roles in early T cell development Celine Dumont, Agnieszka Corsoni-Tadrzak, Sandra Ruf, Jasper de Boer, Adam Williams, Martin Turner, Dimitris Kioussis, and Victor L.J. Tybulewicz* Division of Immune Cell Biology, MRC National Institute for Medical Research, London, United Kingdom Division of Molecular Immunology, MRC National Institute for Medical Research, London, United Kingdom The Babraham Institute, Cambridge, United Kingdom * Corresponding author; email: vtybule{at}nimr.mrc.ac.uk. 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 TCR, 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. M. Routes, W. J. Grossman, J. Verbsky, R. H. Laessig, G. L. Hoffman, C. D. Brokopp, and M. W. Baker Statewide Newborn Screening for Severe T-Cell Lymphopenia JAMA, December 9, 2009; 302(22): 2465 - 2470. [Abstract] [Full Text] [PDF]

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