Erythropoietin induces glycosylphosphatidylinositol hydrolysis - Possible involvement of phospholipase C-gamma(2)

We showed that erythropoietin induced rapid glycosylphosphatidylinositol (G PI) hydrolysis and tyrosine phosphorylation of phospholipase C (PLC)-gamma( 2) in FDC-P1 cells transfected with the wild-type erythropoietin-receptor. Erythropoietin-induced tyrosine phosphorylation of PLC-gamma(2) was time- a nd dose-dependent. By using FDC-P1 cells transfected with an erythropoietin receptor devoid of tyrosine residues, we showed that both effects required the tyrosine residues of intracellular domain on the erythropoietin recept or. Erythropoietin-activated PLC-gamma(2) hydrolyzed purified [H-3]GPI indi cating that GPI hydrolysis and PLC-gamma(2) activation under erythropoietin stimulation were correlated. Results obtained on FDC-P1 cells transfected with erythropoietin receptor mutated on tyrosine residues suggest that tyro sines 343, 401, 464, and/or 479 are involved in erythropoietin-induced GPI hydrolysis and tyrosine phosphorylation of PLC-gamma(2), whereas tyrosines 429 and/or 431 seem to be involved in an inhibition of both effects. Thus, our results suggest that erythropoietin regulates C;PI hydrolysis via tyros ine phosphorylation of its receptor and PLC-gamma(2) activation.