STAT-3 activation is required for normal G-CSF-dependent proliferation and granulocytic differentiation
STAT-3 activation is required for normal G-CSF-dependent proliferation and granulocytic differentiation
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DOI：
10.1016/s1074-7613(01)00101-7
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发表时间：
2001-02-01
期刊：
影响因子：
32.4
通讯作者：
Link, DC
中科院分区：
文献类型：
--
作者：
McLemore, ML;Grewal, S;Link, DC
为了研究信号换能器和转录激活因子（STAT）蛋白在粒细胞集落刺激因子（G-CSF）调节的生物反应中的作用，我们培养了转基因小鼠，其G-CSF受体（称为d715F）的靶向突变可以消除G-CSF依赖性的STAT-3激活并减弱STAT-5激活。纯合子突变小鼠是严重的中性粒细胞减少症，其骨髓中积累了未成熟的髓细胞前体。g - csf诱导的造血祖细胞增殖和粒细胞分化严重受损。在d715F祖细胞中表达一种本构活性形式的STAT-3几乎完全挽救了这些缺陷。相反，野生型祖细胞中STAT-3的显性阴性表达会导致g - csf诱导的增殖和分化受损。这些数据表明，G-CSFR激活STAT-3对于正常增殖信号的转导至关重要，并有助于分化信号的转导。
To investigate the role of signal transducer and activator of transcription (STAT) proteins in granulocyte colony-stimulating factor (G-CSF)-regulated biological responses, we generated transgenic mice with a targeted mutation of their G-CSF receptor (termed d715F) that abolishes G-CSF-dependent STAT-3 activation and attenuates STAT-5 activation. Homozygous mutant mice are severely neutropenic with an accumulation of immature myeloid precursors in their bone marrow. G-CSF-induced proliferation and granulocytic differentiation of hematopoietic progenitors is severely impaired. Expression of a constitutively active form of STAT-3 in d715F progenitors nearly completely rescued these defects. Conversely, expression of a dominant-negative form of STAT-3 in wild-type progenitors results in impaired G-CSF-induced proliferation and differentiation. These data suggest that STAT-3 activation by the G-CSFR is critical for the transduction of normal proliferative signals and contributes to differentiative signals.