Phosphatidylinositol 3-kinase regulates glycosylphosphatidylinositol hydrolysis through PLC-gamma(2) activation in erythropoietin-stimulated cells.
Erythropoietin (Epo)-induced glycosylphosphatidylinositol (GPI) hydrolysis was previously described to be correlated with phospholipase C-gamma 2 (PLC-gamma2) activation. Here, we analyzed the involvement of phosphatidylinositol (PtdIns) 3-kinase in GPI hydrolysis through PLC-gamma2 tyrosine phosphorylation in response to Epo in FDC-P1 cells transfected with a wild type (WT) erythropoietin-receptor (Epo-R). We showed ... that phosphatidylinositol 3-kinase (PtdIns 3-kinase) inhibitor LY294002 inhibits Epo-induced hydrolysis of endogenous GPI and Epo-induced PLC-gamma2 tyrosine phosphorylation in a dose-dependent manner. Wortmannin, another PtdIns 3-kinase inhibitor, also suppressed Epo-induced PLC-gamma2 tyrosine phosphorylation. We also present evidence that PLC-gamma2 translocation to the membrane fraction on Epo stimulation is completely inhibited by LY294002. Upon Epo stimulation, the tyrosine-phosphorylated PLC-gamma2 was found to be associated with the tyrosine-phosphorylated Grb2-associated binder (GAB)2, SHC and SHP2 proteins. LY294002 cell preincubation did not affect GAB2, SHC and SHP2 tyrosine phosphorylation but inhibited the binding of PLC-gamma2 to GAB2 and SHP2. Taken together, these results show that PtdIns 3-kinase controls Epo-induced GPI hydrolysis through PLC-gamma2.
Mesh Terms:
1-Phosphatidylinositol 3-Kinase, Adaptor Proteins, Signal Transducing, Adaptor Proteins, Vesicular Transport, Animals, Cell Differentiation, Cell Division, Cell Membrane, Cells, Cultured, Dose-Response Relationship, Drug, Enzyme Inhibitors, Erythrocytes, Erythroid Precursor Cells, Erythropoietin, Glycosylphosphatidylinositols, Helminth Proteins, Humans, Hydrolysis, Isoenzymes, Phospholipase C gamma, Phosphoproteins, Phosphorylation, Protein Binding, Protein Transport, Proteins, Shc Signaling Adaptor Proteins, Subcellular Fractions, Transfection, Type C Phospholipases, Tyrosine
1-Phosphatidylinositol 3-Kinase, Adaptor Proteins, Signal Transducing, Adaptor Proteins, Vesicular Transport, Animals, Cell Differentiation, Cell Division, Cell Membrane, Cells, Cultured, Dose-Response Relationship, Drug, Enzyme Inhibitors, Erythrocytes, Erythroid Precursor Cells, Erythropoietin, Glycosylphosphatidylinositols, Helminth Proteins, Humans, Hydrolysis, Isoenzymes, Phospholipase C gamma, Phosphoproteins, Phosphorylation, Protein Binding, Protein Transport, Proteins, Shc Signaling Adaptor Proteins, Subcellular Fractions, Transfection, Type C Phospholipases, Tyrosine
Cell. Signal.
Date: Oct. 01, 2002
PubMed ID: 12135708
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