Regulation of phospholipase C-γ2 via phosphatidylinositol 3-kinase in macrophages

Abstract

Phospholipase C-γ (PLC-γ) isoforms are thought to be activated by both tyrosine phosphorylation and phosphatidylinositol 3,4,5 trisphosphate (PtdIns 3,4,5 P 3), the product of phosphatidylinositol 3-kinase (PtdIns 3-kinase). In this study, we show that stimulation of mouse macrophages with either zymosan beads or bacteria ( Prevotella intermedia) induced tyrosine phosphorylation of PLC-γ2. Zymosan stimulation also induced translocation to membrane and cytoskeleton fractions, which was inhibited by the PtdIns 3-kinase inhibitors wortmannin and LY 294002. However, the tyrosine phosphorylation of PLC-γ2 induced by zymosan was not affected by the inhibitors wortmannin and LY 294002. In contrast to zymosan and bacteria, PLC-γ2 was not phosphorylated by stimulation with lipopolysaccharide (LPS), phorbol ester or calcium ionophore. Moreover, the PLC-γ1 isoform was not detected in mouse macrophages. These data indicate that PtdIns 3-kinase is critical for the translocation but not for the tyrosine phosphorylation of PLC-γ2 in mouse macrophages and that the latter may be insufficient for enzyme activation.