Stark G R, Kerr I M, Williams B R, Silverman R H, Schreiber R D
Lerner Research Institute, Cleveland Clinic Foundation, Ohio 44195, USA.
Annu Rev Biochem. 1998;67:227-64. doi: 10.1146/annurev.biochem.67.1.227.
Interferons play key roles in mediating antiviral and antigrowth responses and in modulating immune response. The main signaling pathways are rapid and direct. They involve tyrosine phosphorylation and activation of signal transducers and activators of transcription factors by Janus tyrosine kinases at the cell membrane, followed by release of signal transducers and activators of transcription and their migration to the nucleus, where they induce the expression of the many gene products that determine the responses. Ancillary pathways are also activated by the interferons, but their effects on cell physiology are less clear. The Janus kinases and signal transducers and activators of transcription, and many of the interferon-induced proteins, play important alternative roles in cells, raising interesting questions as to how the responses to the interferons intersect with more general aspects of cellular physiology and how the specificity of cytokine responses is maintained.
干扰素在介导抗病毒和抗生长反应以及调节免疫反应中发挥关键作用。主要的信号通路快速且直接。它们涉及酪氨酸磷酸化以及细胞膜上的Janus酪氨酸激酶对信号转导和转录激活因子的激活,随后信号转导和转录激活因子释放并迁移至细胞核,在细胞核中它们诱导许多决定反应的基因产物的表达。辅助通路也被干扰素激活,但其对细胞生理学的影响尚不清楚。Janus激酶、信号转导和转录激活因子以及许多干扰素诱导蛋白在细胞中发挥重要的替代作用,这就引发了一些有趣的问题,比如对干扰素的反应如何与细胞生理学的更一般方面相互交叉,以及细胞因子反应的特异性是如何维持的。