Protein kinase B (c-Akt), phosphatidylinositol 3-kinase, and STAT5 are activated by erythropoietin (EPO) in HCD57 erythroid cells but are constitutively active in an EPO-independent, apoptosis-resistant subclone (HCD57-SREI cells)
Protein kinase B (c-Akt), phosphatidylinositol 3-kinase, and STAT5 are activated by erythropoietin (EPO) in HCD57 erythroid cells but are constitutively active in an EPO-independent, apoptosis-resistant subclone (HCD57-SREI cells)
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DOI：
10.1182/blood.v93.11.3757.411a34_3757_3773
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发表时间：
1999-06-01
期刊：
影响因子：
20.3
通讯作者：
Sawyer, ST
中科院分区：
文献类型：
--
作者：
Bao, HF;Jacobs-Helber, SM;Sawyer, ST
我们发现促红细胞生成素（EPO）和干细胞因子（SCF）激活EPO依赖的HCD 57红系细胞中的蛋白激酶B（PKB/Akt）。为了更好地理解控制增殖和活力的信号，亚克隆并表征了在不存在EPO的情况下抵抗凋亡的红系细胞（HCD 57-SREI细胞）。在这些EPO非依赖性细胞中观察到PKB/Akt、STAT 5a和STAT 5 b的组成性激活。PI 3-激酶抑制剂LY 294002可阻断PKB/Akt和PKB/Akt的活性，PI 3-激酶是PKB/Akt的上游激活剂。LY 294002研究表明，HCD 57-SREI和HCD 57细胞的增殖和活力与PKB/Akt活性相关; SCF处理HCD 57细胞也激活了PKB/Akt，但不能保护HCD 57细胞免于凋亡，这一结果表明，PKB/PI 3-激酶活性是必要的，但不足以促进活力和/或增殖。通过不包括JAK 2或EPOR的未知途径激活的组成型STAT 5活性可能与组成型PI 3-激酶/PKB/Akt途径协同作用，以保护EPO非依赖性HCD 57-SREI细胞免于凋亡并促进有限的增殖。(C)1999年，美国血液学会。
We found that erythropoietin (EPO) and stem cell factor (SCF) activated protein kinase B (PKB/Akt) in EPO-dependent HCD57 erythroid cells. To better understand signals controlling proliferation and viability, erythroid cells that resist apoptosis in the absence of EPO were subcloned and characterized (HCD57-SREI cells). Constitutive activations of PKB/Akt, STAT5a, and STAT5b were noted in these EPO-independent cells. PIS-kinase activity was an upstream activator of PKB/Akt because the PI3-kinase inhibitor LY294002 blocked both constitutive PKB/Akt and factor-dependent PKB/Akt activity. The LY294002 study showed that proliferation and viability of both HCD57-SREI and HCD57 cells correlated with the activity of PKB/Akt; however, PKB/Akt activity alone did not protect these cells from apoptosis, Treatment of HCD57 cells with SCF also activated PKB/Akt, but did not protect from apoptosis, This result suggested that PKB/PI3-kinase activity is necessary but not sufficient to promote viability and/or proliferation. Constitutive STAT5 activity, activated through an unknown pathway not including JAK2 or EPOR, may act in concert with the constitutive PI3-kinase/PKB/Akt pathway to protect the EPO-independent HCD57-SREI cells from apoptosis and promote limited proliferation. (C) 1999 by The American Society of Hematology.