PMID- 10567359 OWN - NLM STAT- MEDLINE DCOM- 19991229 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 274 IP - 48 DP - 1999 Nov 26 TI - Erythropoietin induces glycosylphosphatidylinositol hydrolysis. Possible involvement of phospholipase c-gamma(2). PG - 33966-72 AB - 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. FAU - Boudot, C AU - Boudot C AD - Laboratoire de Biochimie, CNRS UPRES-A 6021, IFR 53 Biomolecules, UFR Sciences Exactes et Naturelles, BP 1039, Universite de Reims Champagne-Ardenne, F 51687 Reims Cedex 2, France. FAU - Petitfrere, E AU - Petitfrere E FAU - Kadri, Z AU - Kadri Z FAU - Chretien, S AU - Chretien S FAU - Mayeux, P AU - Mayeux P FAU - Haye, B AU - Haye B FAU - Billat, C AU - Billat C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Glycosylphosphatidylinositols) RN - 0 (Isoenzymes) RN - 0 (Receptors, Erythropoietin) RN - 11096-26-7 (Erythropoietin) RN - 42HK56048U (Tyrosine) RN - EC 3.1.4.- (Type C Phospholipases) RN - EC 3.1.4.3 (Phospholipase C gamma) SB - IM MH - Animals MH - Cell Line MH - Erythropoietin/*pharmacology MH - Glycosylphosphatidylinositols/*metabolism MH - Hydrolysis/drug effects MH - Isoenzymes/metabolism MH - Mutation MH - Phospholipase C gamma MH - Phosphorylation/drug effects MH - Receptors, Erythropoietin/chemistry/genetics/metabolism MH - Transfection MH - Type C Phospholipases/metabolism MH - Tyrosine/metabolism EDAT- 1999/11/24 00:00 MHDA- 1999/11/24 00:01 CRDT- 1999/11/24 00:00 PHST- 1999/11/24 00:00 [pubmed] PHST- 1999/11/24 00:01 [medline] PHST- 1999/11/24 00:00 [entrez] AID - 10.1074/jbc.274.48.33966 [doi] AID - S0021-9258(19)53486-X [pii] PST - ppublish SO - J Biol Chem. 1999 Nov 26;274(48):33966-72. doi: 10.1074/jbc.274.48.33966.