Erythropoietin stimulates phosphorylation and activation of GATA-1 via the PI3-kinase/AKT signaling pathway

被引:147
作者
Zhao, W
Kitidis, C
Fleming, MD
Lodish, HF
Ghaffari, S [1 ]
机构
[1] Mt Sinai Sch Med, Dept Gene & Cell Med, Div Hematol Oncol, New York, NY 10029 USA
[2] Mt Sinai Sch Med, Dept Med, Div Hematol Oncol, New York, NY USA
[3] Whitehead Inst Biomed Res, Cambridge, England
[4] Harvard Univ, Sch Med, Childrens Hosp, Dept Pathol, Boston, MA USA
[5] MIT, Dept Biol, Cambridge, MA USA
关键词
D O I
10.1182/blood-2005-06-2516
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Erythropoietin (Epo) stimulation of its receptor's downstream signaling pathways and optimum function of GATA-1 transcription factor are both essential for normal erythroid cell development. Eporeceptor (EpoR) signaling and GATA-1 regulate proliferation, survival, differentiation, and maturation of erythroid cells. Whether any signal that is generated by EpoR targets GATA-1 or affects GATA-1 transcriptional activity is not known. Here, we demonstrate that stimulation of EpoR results in phosphorylation of GATA-1 at serine 310 (S310) in primary fetal liver erythroid progenitors and in cultured erythroid cells. We show that phosphorylation of GATA-1 is important for Epo-induced maturation of fetal liver erythroid progenitor cells. The P13-kinase/AKT signaling pathway is identified as a mediator of Epo-induced phosphorylation of GATA-1. AKT serine threonine kinase phosphorylates GATA-1S310 in vitro and in erythroid cells and enhances GATA-1 transcriptional activity. These data demonstrate that EpoR signaling phosphorylates GATA-1 and modulates its activity via the P13-kinase/AKT signaling pathway.
引用
收藏
页码:907 / 915
页数:9
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