Analysis of Signals and Functions of the Chimeric Human Granuloctye-Macrophage Colony-Stimulating Factor Receptor in BA/F3 Cells and Transgenic Mice
Analysis of Signals and Functions of the Chimeric Human Granuloctye-Macrophage Colony-Stimulating Factor Receptor in BA/F3 Cells and Transgenic Mice
复制标题
BA/F3细胞和转基因小鼠中嵌合人粒细胞-巨噬细胞集落刺激因子受体的信号和功能分析
作者：
S. Watanabe;Yutaka Aoki;I. Nishijima;Ming;Ken‐ichi Arai
GM-CSF、IL-3和IL-5的受体由两个亚基组成：α，对每个细胞因子都有特异性，βc是所有细胞因子共有的。虽然βc在信号转导中的作用已被广泛研究，但α亚基的作用仍有待阐明。为了分析人(h) GM-CSF受体α亚基的作用，我们构建了一个由α的细胞外和跨膜区与βc的细胞质区融合组成的嵌合受体亚基，命名为α/β。在BA/F3细胞中，由α/β，β组成的嵌合受体可转导丝裂原活化蛋白激酶级联激活和增殖信号，以响应hGM-CSF。虽然在hGM-CSF刺激下Jak1磷酸化而Jak2不磷酸化，但显性阴性Jak2抑制c-fos启动子激活，而非显性阴性Jak1。为了确定嵌合受体α/β，β在体内是否具有功能，我们建立了表达嵌合受体α/β，β的转基因小鼠。表达α/β，β受体的转基因小鼠骨髓细胞在GM- csf的作用下不仅能形成GM集落，还能形成不同谱系的集落。此外，用hGM-CSF培养转基因小鼠骨髓细胞可产生肥大细胞。因此，即使在骨髓细胞中，α亚基的细胞质区域似乎也不是hGM-CSF促进活性所必需的。
Receptors for GM-CSF, IL-3, and IL-5 are composed of two subunits: α, which is specific for each cytokine, and βc, which is shared by all. Although the role of βc in signal transduction has been extensively studied, the role of the α subunit has remained to be clarified. To analyze the role of the human (h) GM-CSF receptor α subunit, we constructed a chimeric receptor subunit composed of extracellular and transmembrane regions of α fused with the cytoplasmic region of βc, designated α/β. In BA/F3 cells, chimeric receptor composed of α/β,β can transduce signals for mitogen-activated protein kinase cascade activation and proliferation in response to hGM-CSF. Although phosphorylation of Jak1 but not of Jak2 occurred with stimulation of hGM-CSF, the dominant-negative Jak2 but not the dominant-negative Jak1 suppresses c-fos promoter activation. To determine whether the chimeric receptor α/β,β is functional in vivo, we developed transgenic mice expressing the chimeric receptor α/β,β. Bone marrow cells from the transgenic mice expressing the α/β,β receptor form not only GM colonies but also various lineages of colonies in response to GM-CSF. In addition, mast cells were produced when bone marrow cells of the transgenic mouse were cultured with hGM-CSF. Thus, it appears that the cytoplasmic region of the α subunit is not required for hGM-CSF promoting activities, even in bone marrow cells.
人粒细胞-巨噬细胞集落刺激因子受体 α 亚基在 JAK2 和 STAT5 激活中作用的表征。
影响因子：
20.3
作者：
Doyle,SE;Gasson,JC
通讯作者：
Gasson,JC
低亲和力嵌合人α/β粒细胞巨噬细胞集落刺激因子受体在小鼠细胞系中诱导配体依赖性增殖。
DOI：
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发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Eder,M;Ernst,TJ;Ganser,A;Jubinsky,PT;Inhorn,R;Hoelzer,D;Griffin,JD
通讯作者：
Griffin,JD
影响因子：
20.3
作者：
Socolovsky, M;Fallon, AEJ;Lodish, HF
通讯作者：
Lodish, HF