Vav1 promotes T cell cycle progression by linking TCR/CD28 costimulation to FOXO1 and p27kip1 expression

Céline Charvet, Ann Janette Canonigo, Stéphane Bécart, Ulrich Maurert, Ana V. Miletic, Wojciech Swat, Marcel Deckert, Amnon Altman

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


Vav proteins play a critical role in T cell activation and proliferation by promoting cytoskeleton reorganization, transcription factor activation, and cytokine production. In this study, we investigated the role of Vav in T cell cycle progression. TCR/CD28-stimulated Vav1-/- T cells displayed a cell cycle block at the G0-G1 stage, which accounted tor their defective proliferation. This defect was associated with impaired TCR/CD28-induced phosphorylation of Akt and the Forkhead family transcription factor, FOXO1. The cytoplasmic localization of FOXO1 and its association with 14-3-3τ were also reduced in Vav1-/- T cells. Consistent with the important role of FOXO1 in p27kip1 transcription, stimulated Vav1-/- T cells falled to down-regulate the expression of p27 kip1, explaining their G0-G1 arrest. These defects were more pronounced in Vav1/Vav3 double-deficient T cells, suggesting partial redundancy between Vav1 and Vav3. Importantly, IL-2-induced p27 kip1 down-regulation and cyclin D3 up-regulation and FOXO1 phosphorylation were similar in Vav1-/- and wild-type T lymphoblasts, indicating that defective FOXO1 phosphorylation and p27kip1 and cyclin D3 expression do not result from deficient IL-2 signaling in the absence of Vav1. Thus, Vav1 is a critical regulator of a PI3K/Akt/FOXO1 pathway, which controls T cell cycle progression and proliferation.

Original languageEnglish
Pages (from-to)5024-5031
Number of pages8
JournalJournal of Immunology
Issue number8
StatePublished - Oct 15 2006


Dive into the research topics of 'Vav1 promotes T cell cycle progression by linking TCR/CD28 costimulation to FOXO1 and p27kip1 expression'. Together they form a unique fingerprint.

Cite this