| First Author | Tassi I | Year | 2007 |
| Journal | Immunity | Volume | 27 |
| Issue | 2 | Pages | 214-27 |
| PubMed ID | 17723215 | Mgi Jnum | J:124330 |
| Mgi Id | MGI:3721339 | Doi | 10.1016/j.immuni.2007.07.014 |
| Citation | Tassi I, et al. (2007) p110gamma and p110delta Phosphoinositide 3-Kinase Signaling Pathways Synergize to Control Development and Functions of Murine NK Cells. Immunity 27(2):214-27 |
| abstractText | Phosphoinositide 3-kinases (PI-3Ks) are key enzymes for cell development, activation, and survival. Here we showed that PI-3K class IB and class IA catalytic subunits, p110gamma and p110delta, played a crucial role in the development and functions of murine NK cells. p110gamma deficiency and impairment of G protein-coupled receptor (GPRC) signaling prevented full NK cell maturation. Concomitant loss of p110gamma and p110delta exacerbated this defect, resulting in a very small population of NK cells with a highly immature phenotype in the bone marrow and periphery. Moreover, combined p110gamma and p110delta signals were required for cytotoxicity and activation of the kinase ERK during NK cell-target cell interaction. p110gamma played a major role in receptor-induced interferon-gamma (IFN-gamma) production through a pathway that involved the kinase ERK and 5-Lipoxigenase, which most likely generates lipid mediators activating GPRCs. Conversely, PI3Ks negatively regulated interleukin-12 (IL-12) and IL-18-induced IFN-gamma by modulating p38 kinase activation. Our data shed light on the multiple intersecting pathways through which PI3Ks control NK cell-mediated innate responses. |
