Novak U, Ward A C, Hertzog P J, Hamilton J A, Paradiso L
University of Melbourne, Dept. of Medicine, Royal Melbourne Hospital, Parkville, Australia.
Growth Factors. 1996;13(3-4):251-60. doi: 10.3109/08977199609003226.
There is evidence that the cellular responses to cytokines, such as granulocyte colony stimulating factor (G-CSF) and interferons, depend on prior activation of components of the JAK/STAT signalling pathway. We report here that the myeloid cell line NFS-60 shows aberrant JAK/STAT signalling yet elicits expected biological responses to G-CSF and interferons-alpha/beta and gamma. Instead of increased phosphorylation of JAK1 and JAK2 in response to G-CSF and interferon-gamma, and JAK1 and Tyk2 in response to interferon-alpha/beta, we observed only an increase of phosphorylation of Tyk2 in response to all of these cytokines in NFS-60 cells. The subset of STAT proteins being activated in response to these cytokines was unusual as well. G-CSF activated STAT3 and STAT5A, whereas interferons activated, in addition to STAT1 and STAT5 other, as yet unidentified, DNA binding proteins. However, NFS-60 cells show normal biological responses to these cytokines, such as proliferation in response to G-CSF, and reduction of proliferation, induction of an anti-viral response and induction of specific genes in response to interferons.
有证据表明，细胞对细胞因子（如粒细胞集落刺激因子（G-CSF）和干扰素）的反应取决于JAK/STAT信号通路组分的预先激活。我们在此报告，髓系细胞系NFS-60显示出异常的JAK/STAT信号传导，但对G-CSF和α/β及γ干扰素引发预期的生物学反应。在NFS-60细胞中，我们没有观察到G-CSF和γ干扰素刺激下JAK1和JAK2磷酸化增加，以及α/β干扰素刺激下JAK1和Tyk2磷酸化增加，而是仅观察到所有这些细胞因子刺激下Tyk2磷酸化增加。响应这些细胞因子而被激活的STAT蛋白亚群也不寻常。G-CSF激活STAT3和STAT5A，而干扰素除了激活STAT1和STAT5外，还激活其他尚未鉴定的DNA结合蛋白。然而，NFS-60细胞对这些细胞因子表现出正常的生物学反应，如对G-CSF的增殖反应，以及对干扰素的增殖减少、抗病毒反应诱导和特定基因诱导。
