Wortmannin, a specific inhibitor of phosphatidylinositol-3-kinase, inhibits erythropoietin-induced erythroid differentiation of K562 cells.
To elucidate the role of phosphatidylinositol-3-kinase (Pl3K) in erythropoietin receptor (EPOR)-mediated signaling, we examined the effects of wortmannin (WT), a specific inhibitor of Pl3K on the proliferation of erythropoietin (EPO)-induced erythroid differentiation in K562 human erythroleukemia cells. Percentage of benzidine-positive cells synthesizing hemoglobin and level of glycophorin A expression in the cells were increased after EPO treatment. EPO-enhanced Pl3K activity was suppressed by WT treatment in a dose-dependent manner and constant inhibition of Pl3K by WT interfered with both hemoglobin synthesis and glycophorin A expression promoted by EPO. Wortmannin, however, did not inhibit hemin-induced erythroid differentiation. These findings in the present study suggest that Pl3K plays a crucial role in the transducing the erythroid differentiation signal through EPOR activated by EPO-binding ib K562 cells and that the signaling pathways involved in EPO-induced erythroid differentiation differ from those involved in hemin-induced differentiation.
Kubota
Y
Y
Kagawa Medical School, Japan.
Tanaka
T
T
Yamaoka
G
G
Yamaguchi
M
M
Ohnishi
H
H
Kawanishi
K
K
Takahara
J
J
Irino
S
S
D000730:Androstadienes / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004921:Erythropoietin / Q000494:pharmacology*; D015870:Gene Expression; D006021:Glycophorins / Q000096:biosynthesis; D006418:Heme / Q000494:pharmacology; D006454:Hemoglobins / Q000096:biosynthesis*; D006801:Humans; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D004921:Erythropoietin; D006021:Glycophorins; D006418:Heme; D006454:Hemoglobins; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011994:Recombinant Proteins; D000077191:Wortmannin