A critical role for the cytoplasmic domain of the granulocyte-macrophage colony-stimulating factor alpha receptor in mediating cell growth.
A critical role for the cytoplasmic domain of the granulocyte-macrophage colony-stimulating factor alpha receptor in mediating cell growth.
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发表时间：
1993-06
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通讯作者：
A. Polotskaya;Y. Zhao;M. Lilly;A. Kraft
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作者：
A. Polotskaya;Y. Zhao;M. Lilly;A. Kraft
人粒细胞-巨噬细胞集落刺激因子 (GM-CSF) 受体由结合 GM-CSF 的 α 亚基和允许高亲和力结合的 β 亚基组成。为了研究α受体的短胞质尾部（54个氨基酸）在介导信号转导和控制细胞生长中的作用，我们在α受体跨膜结构域后放置终止密码子，并在鼠Ba/F3细胞中表达该受体。与完整的α亚基不同，这种缩短的受体无法刺激蛋白质磷酸化或介导进入细胞周期。通过将表达α和β受体的Ba/F3细胞与表达α或终止α受体的Ba/F3细胞进行比较，我们已经能够将特定的GM-CSF诱导的事件与细胞周期定向相关联。我们发现细胞生长与 c-myc、pim-1 和 cyclin D2 mRNA 细胞水平的长期增加相关，但与即早期基因或丝裂原激活蛋白激酶磷酸化的变化无关。这表明 GM-CSF 激活了非已知磷蛋白介导的其他信号转导途径。由于人白介素 3 和 5 共有 β 受体，因此我们的数据表明，对 GM-CSF 反应的特异性部分是由 α 受体亚基的短胞质尾介导的。
The human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor is composed of an alpha subunit which binds GM-CSF and a beta subunit which allows for high affinity binding. To investigate the role of the short cytoplasmic tail (54 amino acids) of the alpha receptor in mediating signal transduction and in controlling cell growth, we placed a stop codon after the alpha receptor transmembrane domain and expressed this receptor in murine Ba/F3 cells. Unlike the complete alpha subunit, this shortened receptor was unable to stimulate protein phosphorylation or mediate entry into the cell cycle. By comparing Ba/F3 cells expressing the alpha and beta receptors with those expressing the alpha or the terminated alpha receptor, we have been able to correlate specific GM-CSF-induced events with cell cycle commitment. We find that cell growth is correlated with prolonged increases in the cell levels of c-myc, pim-1, and cyclin D2 mRNAs, but not with changes in either immediate early genes or mitogen-activated protein kinase phosphorylation. This suggests that additional signal transduction pathways not mediated by known phosphoproteins are activated by GM-CSF. Since the beta receptor is shared by human interleukins 3 and 5, our data suggest that the specificity of response to GM-CSF is mediated in part by the short cytoplasmic tail of the alpha receptor subunit.