Inhibition of T-cell activation by PIK3IP1.

The PI-3 kinase (PI3K) pathway is critical for T-cell development and activation. Several negative regulators of this pathway have already been described and characterized: the lipid phosphatases SHIP, inositol polyphosphate-4-phosphatase, type II (INPP4B), and phosphatase and tensin homolog (PTEN), the latter of which are tumor suppressors. PIK3IP1 (PI3K interacting protein 1) is a recently described transmembrane protein that has the ability to bind the catalytic protein p110 and prevent its activation by the p85 family adaptor proteins. Thus far, nothing is known about the possible role of PIK3IP1 in the regulation of lymphocyte development or activation. Here, we show for the first time that PIK3IP1 is expressed in T cells. Ectopic expression of PIK3IP1 in Jurkat or D10 T-cell lines inhibited activation of an NFAT/AP-1 transcriptional reporter. Conversely, siRNA-mediated silencing of PIK3IP1 in the same cell lines modestly augmented Akt phosphorylation, T-cell activation, and production of IL-2. These results suggest that the novel PI3K regulator PIK3IP1 plays an inhibitory role in T-cell activation.