Erythropoietin induces glycosylphosphatidylinositol hydrolysis. Possible involvement of phospholipase c-gamma(2).
We showed that erythropoietin induced rapid glycosylphosphatidylinositol (GPI) 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- and 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 receptor. Erythropoietin-activated PLC-gamma(2) hydrolyzed purified [(3)H]GPI indicating 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 tyrosines 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 GPI hydrolysis via tyrosine phosphorylation of its receptor and PLC-gamma(2) activation.
Boudot
C
C
Laboratoire de Biochimie, CNRS UPRES-A 6021, IFR 53 Biomolécules, UFR Sciences Exactes et Naturelles, BP 1039, Université de Reims Champagne-Ardenne, F 51687 Reims Cedex 2, France.
Petitfrère
E
E
Kadri
Z
Z
Chretien
S
S
Mayeux
P
P
Haye
B
B
Billat
C
C
D000818:Animals; D002460:Cell Line; D004921:Erythropoietin / Q000494:pharmacology*; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D006868:Hydrolysis / Q000187:drug effects; D007527:Isoenzymes / Q000378:metabolism; D009154:Mutation; D051966:Phospholipase C gamma; D010766:Phosphorylation / Q000187:drug effects; D017467:Receptors, Erythropoietin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D017261:Glycosylphosphatidylinositols; D007527:Isoenzymes; D017467:Receptors, Erythropoietin; D004921:Erythropoietin; D014443:Tyrosine; D010738:Type C Phospholipases; D051966:Phospholipase C gamma