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

来源：

BLOOD | 2006年 / 107卷 / 03期

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

页码：907 / 915

页数：9

共 72 条

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