Inositol Phospholipid Signaling and the Biology of Natural Killer Cells

A family of phosphoinositide-3 kinase (PI3K) isoenzymes catalyzes the production of second messengers that recruit critical regulators of cell growth, survival, proliferation and motility. Conversely, 3'-(phosphatase and tensin homolog) and 5'-inositol polyphosphatases (SH2-containing inositol phosphatases 1/2, SHIP1/2) are recruited to sites of PI3K signaling at the plasma membrane to oppose or, in some cases, to modify and enhance PI3K signaling. A substantial and growing body of literature demonstrates that these enzymes which mediate interchange of phosphates on inositol phospholipid species at the plasma membrane have prominent roles in natural killer cell biology, including development, effector functions and trafficking. Here, we review the salient points of these recent papers with a special emphasis on the role of p110δ and SHIP1 in natural killer cells.