Constitutively active STAT5 variants induce growth and survival of hematopoietic cells through a PI 3-kinase/Akt dependent pathway
Constitutively active STAT5 variants induce growth and survival of hematopoietic cells through a PI 3-kinase/Akt dependent pathway
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DOI：
10.1038/sj.onc.1204308
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发表时间：
2001-04-19
期刊：
影响因子：
8
通讯作者：
Gouilleux, F
中科院分区：
文献类型：
--
作者：
Constantino, S;Santos, R;Gouilleux, F
信号转导子和转录激活子（STATs）是细胞因子和生长因子诱导的信号转导的重要介质，STAT 5A和STAT 5 B已被证明在体外和体内造血细胞的存活和增殖中起作用，并有助于由TEL-JAK 2癌蛋白转化的细胞的生长和活力。我们研究了组成型活性STAT 5蛋白诱导表达显性阳性STAT 5A或STAT 5 B变体或TEL-JAK 2或TEL-ABL融合蛋白的Ba/F3细胞系的细胞增殖和存活的分子机制。我们的研究结果表明，活化的STAT 5与PT 3-kinase的调节亚基p85组成性相互作用，在这些细胞中观察到PI 3-kinase/Akt通路的组成性活性，并且其细胞周期进程是必需的。相反，虽然PI 3-激酶/Akt途径的活性是表达组成型活性形式的STAT 5A或STAT 5 B的Ba/F3细胞的存活所需的，但是对于由TEL-JAK 2或TEL-ABL融合蛋白转化的细胞，PI 3-激酶/Akt途径的活性是必需的，这表明在这些转化的细胞中发生了另外的存活途径。
Signal Transducer and Activator of Transcription (STATs) are important mediators of cytokine and growth factor-induced signal transduction, STAT5A and STAT5B have been shown to play a role in survival and proliferation of hematopoietic cells both in vitro and in viro and to contribute to the growth and viability of cells transformed by the TEL-JAK2 oncoprotein, In this study, we investigated the molecular mechanisms by which constitutively active STAT5 proteins induce cell proliferation and survival of Ba/F3 cell lines expressing either dominant positive STAT5A or STAT5B variants or TEL-JAK2 or TEL-ABL fusion proteins. Our results showed that active STAT5 constitutively interacted with p85, the regulatory subunit of the PT 3-kinase, A constitutive activity of the PI 3-kinase/Akt pathway was observed in these cells and required for their cell cycle progression. In contrast, while activity of the PI 3-kinase/Akt pathway was required for survival of Ba/F3 cells expressing the constitutively active forms of STAT5A or STAT5B, it was dispensable for cells transformed by TEL-JAK2 or TEL-ABL fusion proteins, suggesting that additional survival pathways take place in these transformed cells.