Notch1 and Notch2 inhibit myeloid differentiation in response to different cytokines
Notch1 and Notch2 inhibit myeloid differentiation in response to different cytokines
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DOI：
10.1128/mcb.18.4.2324
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发表时间：
1998-04-01
影响因子：
5.3
通讯作者：
Milner, LA
中科院分区：
文献类型：
--
作者：
Bigas, A;Martin, DIK;Milner, LA
我们比较了两种哺乳动物Notch同源物（小鼠Notch1和Notch2）抑制32D骨髓祖细胞粒细胞分化的能力，32D细胞在粒细胞集落刺激因子（G-CSF）或粒细胞巨噬细胞集落刺激因子（gmcsf）刺激下均发生粒细胞分化。活化的细胞内结构域Notch1的表达抑制G-CSF诱导的分化，而不抑制GM-CSF诱导的分化；相反，Notch2的相应结构域对GM-CSF的分化有抑制作用，而对G-CSF则无抑制作用。Notch的cdc10结构域的c端区域赋予cdc10结构域的细胞因子特异性，Notch1和Notch2的细胞因子反应模式随该区域转移，我们将其称为Notch细胞因子反应（NCR）区域。NCR区域还与不同Notch分子的翻译后修饰和亚细胞定位的差异有关。这些发现表明，哺乳动物中发现的多种形式的Notch具有结构差异，从而允许它们的功能被特异性分化信号调节。
We have compared the ability of two mammalian Notch homologs, mouse Notch1 and Notch2, to inhibit the granulocytic differentiation of 32D myeloid progenitor cells, 32D cells undergo granulocytic differentiation when stimulated with either granulocyte colony-stimulating factor (G-CSF) or granulocyte macrophage colony-stimulating factor (GM-CSF). Expression of the activated intracellular domain of Notch1 inhibits the differentiation induced by G-CSF but not by GM-CSF; conversely, the corresponding domain of Notch2 inhibits differentiation in response to GM-CSF but not to G-CSF, The region immediately C-terminal to the cdc10 domain of Notch confers cytokine specificity on the cdc10 domain, The cytokine response patterns of Notch1 and Notch2 are transferred with this region, which we have termed the Notch cytokine response (NCR) region. The NCR region is also associated with differences in posttranslational modification and subcellular localization of the different Notch molecules. These findings suggest that the multiple forms of Notch found in mammals have structural differences that allow their function to be modulated by Specific differentiation signals.