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#18713968   2008/08/20 Save this To Up

FOXO1 regulates L-Selectin and a network of human T cell homing molecules downstream of phosphatidylinositol 3-kinase.

In T cells, the PI3K pathway promotes proliferation and survival induced by Ag or growth factors, in part by inactivating the FOXO transcription factor 1. We now report that FOXO1 controls the expression of L-selectin, an essential homing molecule, in human T lymphocytes. This control is already operational in unprimed T cells and involves a transcriptional regulation process that requires the FOXO1 DNA-binding domain. Using transcriptional profiling, we demonstrate that FOXO1 also increases transcripts of EDG1 and EDG6, two sphingosine-1-phosphate receptors that regulate lymphocyte trafficking. Additionally, FOXO1 binds the promoter of the cell quiescence and homing regulator Kr├╝ppel-like factor 2 and regulates its expression. Together, these results reveal a new function of FOXO1 in the immune system and suggest that PI3K controls a coordinated network of transcription factors regulating both cell quiescence and homing of human T lymphocytes.

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#12401211   2002/10/28 Save this To Up

Tandem genomic arrangement of a G protein (Gna15) and G protein-coupled receptor (s1p(4)/lp(C1)/Edg6) gene.

A genomic analysis of the s1p(4)/lp(C1)/Edg6 mouse sphingosine-1-phosphate (S1P) G protein-coupled receptor gene revealed it to be located on central chromosome 10 and to consist of two exons with an intronless coding region. Surprisingly, we found the gene encoding the promiscuously coupling G(alpha15) protein (Gna15) located in tandem just upstream, an arrangement conserved in the human genome (on chromosome 19p13.3). Given that Northern blots demonstrated similar tissue distributions of the mouse s1p(4) and Gna15 transcripts, we propose that transcription of the two genes may be under control of the same enhancer elements and that their protein products may couple in vivo.

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