Ligand-dependent transformation by the receptor for human granulocyte/macrophage colony-stimulating factor and tyrosine phosphorylation of the receptor beta subunit.
Ligand-dependent transformation by the receptor for human granulocyte/macrophage colony-stimulating factor and tyrosine phosphorylation of the receptor beta subunit.
复制标题
人粒细胞/巨噬细胞集落刺激因子受体的配体依赖性转化和受体β亚基的酪氨酸磷酸化。
DOI：
10.1073/pnas.90.9.3963
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发表时间：
1993
影响因子：
11.1
通讯作者：
Feldman,RA
中科院分区：
文献类型：
--
作者：
Areces,LB;Jücker,M;SanMiguel,JA;Mui,A;Miyajima,A;Feldman,RA
人粒细胞/巨噬细胞集落刺激因子（hGMR）的受体由两个亚基α和β组成，这两个亚基都是配体高亲和力结合所必需的。为了检测hGMR的转化潜力，我们将编码受体α和β亚基的cDNA转染到NIH 3 T3细胞中，该细胞通常不表达GMR。将受体亚基引入这些细胞中导致局部转化，这依赖于培养基中人粒细胞/巨噬细胞集落刺激因子（hGM-CSF）的存在。当用其他生长因子如人表皮生长因子或人白细胞介素3替代hGM-CSF时，或当用单独的α或β亚基转染细胞时，未观察到转化。转染后分离的单个条件转化体表达功能性hGMR，对皮摩尔水平的配体转化敏感，并且能够在hGM-CSF存在下但不存在下在软琼脂中锚定非依赖性生长。生物化学分析表明，用hGM-CSF处理这些细胞引起酪氨酸残基上的β亚基和其他细胞蛋白的快速磷酸化，重现了骨髓细胞中GM-CSF信号传导期间发生的一些事件。我们的结论是，共表达的α和β亚基的hGMR在建立小鼠成纤维细胞是足够的重建功能受体，这是能够引起配体依赖性转化。hGMR的致癌潜力支持其失调或异常表达可能在白血病发生中起作用的假设。
The receptor for human granulocyte/macrophage colony-stimulating factor (hGMR) is composed of two subunits, alpha and beta, which are both required for high-affinity binding of the ligand. To examine the transforming potential of hGMR, we have transfected cDNAs encoding the receptor alpha and beta subunits into NIH 3T3 cells, which normally do not express GMRs. Introduction of the receptor subunits into these cells resulted in focal transformation, which was dependent on the presence of human granulocyte/macrophage colony-stimulating factor (hGM-CSF) in the culture medium. No transformation was observed when hGM-CSF was replaced with other growth factors such as human epidermal growth factor or human interleukin 3 or when cells were transfected with the alpha or beta subunit alone. Individual conditional transformants isolated after transfection expressed functional hGMRs, were susceptible to transformation by picomolar levels of the ligand, and were capable of anchorage-independent growth in soft agar in the presence but not in the absence of hGM-CSF. Biochemical analysis showed that treatment of these cells with hGM-CSF caused a rapid phosphorylation of the beta subunit and other cellular proteins on tyrosine residues, recapitulating some of the events that take place during GM-CSF signaling in myeloid cells. We conclude that coexpression of the alpha and beta subunits of hGMR in established murine fibroblasts is sufficient to reconstitute a functional receptor, which is capable of causing ligand-dependent transformation. The oncogenic potential of hGMR lends support to the hypothesis that its deregulated or abnormal expression may play a role in leukemogenesis.