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, Victor L.J. Tybulewicz

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)3990-3998
Number of pages9
JournalUnknown Journal
Issue number17
StatePublished - 2009

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology


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