| First Author | Rojas JM | Year | 2016 |
| Journal | J Leukoc Biol | Volume | 100 |
| Issue | 6 | Pages | 1285-1296 |
| PubMed ID | 27381007 | Mgi Jnum | J:318382 |
| Mgi Id | MGI:6859448 | Doi | 10.1189/jlb.1A1215-541RR |
| Citation | Rojas JM, et al. (2016) PI3K p85 beta regulatory subunit deficiency does not affect NK cell differentiation and increases NKG2D-mediated activation. J Leukoc Biol 100(6):1285-1296 |
| abstractText | Activation of NK cells depends on a balance between activating and inhibitory signals. Class Ia PI3K are heterodimeric proteins with a catalytic and a regulatory subunit and have a central role in cell signaling by associating with tyrosine kinase receptors to trigger signaling cascades. The regulatory p85 subunit participates in signaling through NKG2D, one of the main activating receptors on NK cells, via its interaction with the adaptor protein DAP10. Although the effects of inhibiting catalytic subunits or deleting the regulatory p85alpha subunit have been studied, little attention has focused on the role of the p85beta subunit in NK cells. Using p85beta knockout mice, we found that p85beta deficiency does not alter NK cell differentiation and maturation in spleen or bone marrow. NK cells from p85beta(-/-) mice nonetheless produced more IFN-gamma and degranulated more effectively when stimulated with anti-NKG2D antibody. These cells also degranulated and killed NKG2D ligand-expressing target cells more efficiently. We show that p85beta deficiency impaired NKG2D internalization, which could contribute to the activated phenotype. Decreasing p85beta subunit protein levels might thus constitute a therapeutic target to promote NK cell activity toward NKG2D ligand-expressing cells. |
