Regulation of phospholipase C-gamma 2 via phosphatidylinositol 3-kinase in macrophages.
Phospholipase C-gamma (PLC-gamma) 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-gamma 2. 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-gamma 2 induced by zymosan was not affected by the inhibitors wortmannin and LY 294002. In contrast to zymosan and bacteria, PLC-gamma 2 was not phosphorylated by stimulation with lipopolysaccharide (LPS), phorbol ester or calcium ionophore. Moreover, the PLC-gamma 1 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-gamma 2 in mouse macrophages and that the latter may be insufficient for enzyme activation.
Hiller
Gösta
G
Department of Cell and Molecular Biology, B11, Biomedical Centre, Lund University, SE-221 84 Lund, Sweden.
Sundler
Roger
R
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D003599:Cytoskeleton / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007527:Isoenzymes / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051966:Phospholipase C gamma; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D018713:Prevotella intermedia; D021381:Protein Transport; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism*; D000077191:Wortmannin; D015054:Zymosan / Q000494:pharmacology
D000730:Androstadienes; D002867:Chromones; D007527:Isoenzymes; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051966:Phospholipase C gamma; D019000:Phosphotyrosine; D010738:Type C Phospholipases; D000077191:Wortmannin; D015054:Zymosan; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one