Journal
JOURNAL OF IMMUNOLOGY
Volume 190, Issue 2, Pages 748-755Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1201174
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Funding
- INSERM
- Centre National de la Recherche Scientifique
- Ligue Nationale Contre le Cancer
- European Research Council Grant Neurotrafficking [261079]
- Ministry of Research and Higher Education
- Association pour la Recherche sur le Cancer
- European Research Council (ERC) [261079] Funding Source: European Research Council (ERC)
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Forkhead box O (FOXO) transcription factors favor both T cell quiescence and trafficking through their control of the expression of genes involved in cell cycle progression, adhesion, and homing. In this article, we report that the product of the fam65b gene is a new transcriptional target of FOXO1 that regulates RhoA activity. We show that family with sequence similarity 65 member b (Fam65b) binds the small GTPase RhoA via a noncanonical domain and represses its activity by decreasing its GTP loading. As a consequence, Fam65b negatively regulates chemokine-induced responses, such as adhesion, morphological polarization, and migration. These results show the existence of a new functional link between FOXO1 and RhoA pathways, through which the FOXO1 target Fam65b tonically dampens chemokine-induced migration by repressing RhoA activity. The Journal of Immunology, 2013, 190: 748-755.
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