Involvement of the Src kinase Lyn in phospholipase C-gamma 2 phosphorylation and phosphatidylinositol 3-kinase activation in Epo signalling.
We examined the role of the Src kinase Lyn in phospholipase C-gamma 2 (PLC-gamma 2) and phosphatidylinositol (PI) 3-kinase activation in erythropoietin (Epo)-stimulated FDC-P1 cells transfected with a wild type (WT) Epo-receptor (Epo-R). We showed that two inhibitors of Src kinases, PP1 and PP2, abolish both PLC-gamma 2 tyrosine phosphorylation and PI 3-kinase activity in WT Epo-R FDC-P1 cells. We also demonstrated that Epo-phosphorylated Lyn is associated with tyrosine phosphorylated PLC-gamma 2 and PI 3-kinase in WT Epo-R FDC-P1-stimulated cells. Moreover Epo-activated Lyn phosphorylates in vitro PLC-gamma 2 immunoprecipitated from unstimulated cells. Our results suggest that the Src kinase Lyn is involved in PLC-gamma 2 phosphorylation and PI 3-kinase activation induced by Epo.
Boudot
Cédric
C
Laboratoire de Biochimie, CNRS FRE 2534, IFR 53 Biomolécules, UFR Sciences Exactes et Naturelles, BP 1039, Université de Reims Champagne-Ardenne, 51687 Reims Cedex 2, France.
Dassé
Emilie
E
Lambert
Elise
E
Kadri
Zahra
Z
Mayeux
Patrick
P
Chrétien
Stany
S
Haye
Bernard
B
Billat
Claudine
C
Petitfrère
Emmanuelle
E
D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation; D004921:Erythropoietin / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051966:Phospholipase C gamma; D010766:Phosphorylation; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000502:physiology*
D007527:Isoenzymes; D004921:Erythropoietin; D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma