Polotskaya A, Zhao Y, Lilly M L, Kraft A S
Division of Hematology/Oncology, University of Alabama, Birmingham 35294.
Cell Growth Differ. 1993 Jun;4(6):523-31.
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.
人粒细胞-巨噬细胞集落刺激因子（GM-CSF）受体由一个结合GM-CSF的α亚基和一个实现高亲和力结合的β亚基组成。为了研究α受体短细胞质尾（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了一个终止密码子，并在小鼠Ba/F3细胞中表达了该受体。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或截短α受体的细胞进行比较，我们能够将特定的GM-CSF诱导事件与细胞周期进程相关联。我们发现细胞生长与c-myc、pim-1和细胞周期蛋白D2 mRNA细胞水平的长期增加相关，但与即时早期基因或丝裂原活化蛋白激酶磷酸化的变化无关。这表明GM-CSF激活了不由已知磷蛋白介导的其他信号转导途径。由于β受体为人白细胞介素3和5所共有，我们的数据表明对GM-CSF反应的特异性部分由α受体亚基的短细胞质尾介导。
