Phosphatidylinositol 3-kinase regulates glycosylphosphatidylinositol hydrolysis through PLC-γ2 activation in erythropoietin-stimulated cells

Autor: Emmanuelle Petitfrère, Stany Chrétien, Claudine Billat, Zahra Kadri, Patrick Mayeux, Cédric Boudot, Elise Lambert, Bernard Haye
Rok vydání: 2002
Předmět:
Erythrocytes
Src Homology 2 Domain-Containing
Transforming Protein 1
Glycosylphosphatidylinositols
GAB2
Transfection
Wortmannin
Phosphatidylinositol 3-Kinases
chemistry.chemical_compound
hemic and lymphatic diseases
Animals
Humans
LY294002
Phosphatidylinositol
Enzyme Inhibitors
Phosphorylation
Erythropoietin
Cells
Cultured
Adaptor Proteins
Signal Transducing
Erythroid Precursor Cells
Dose-Response Relationship
Drug
biology
Phospholipase C gamma
Kinase
Hydrolysis
Cell Membrane
Proteins
Cell Differentiation
Tyrosine phosphorylation
Helminth Proteins
Cell Biology
Phosphoproteins
Molecular biology
Isoenzymes
Adaptor Proteins
Vesicular Transport
Protein Transport
Shc Signaling Adaptor Proteins
chemistry
Type C Phospholipases
biology.protein
Tyrosine
Cell Division
Platelet-derived growth factor receptor
Protein Binding
Subcellular Fractions
Zdroj: Cellular Signalling. 14:869-878
ISSN: 0898-6568
DOI: 10.1016/s0898-6568(02)00036-0
Popis: 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.
Databáze: OpenAIRE
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