Shuai K, Schindler C, Prezioso V R, Darnell J E
Rockefeller University, New York, NY 10021.
Science. 1992 Dec 11;258(5089):1808-12. doi: 10.1126/science.1281555.
Interferon-gamma (IFN-gamma) induces the transcription of the gene encoding a guanylate binding protein by activating a latent cytoplasmic factor, GAF (gamma-activated factor). GAF is translocated to the nucleus and binds a DNA element, the gamma-activated site. Through cross-linking and the use of specific antibodies GAF was found to be a 91-kilodalton DNA binding protein that was previously identified as one of four proteins in interferon-stimulated gene factor-3 (ISGF-3), a transcription complex activated by IFN-alpha. The IFN-gamma-dependent activation of the 91-kilodalton DNA binding protein required cytoplasmic phosphorylation of the protein on tyrosine. The 113-kilodalton ISGF-3 protein that is phosphorylated in response to IFN-alpha was not phosphorylated nor translocated to the nucleus in response to IFN-gamma. Thus the two different ligands result in tyrosine phosphorylation of different combinations of latent cytoplasmic transcription factors that then act at different DNA binding sites.
γ干扰素（IFN-γ）通过激活一种潜在的细胞质因子GAF（γ激活因子）来诱导编码鸟苷酸结合蛋白的基因转录。GAF转位至细胞核并结合一个DNA元件，即γ激活位点。通过交联和使用特异性抗体，发现GAF是一种91千道尔顿的DNA结合蛋白，它先前被鉴定为干扰素刺激基因因子-3（ISGF-3）中的四种蛋白之一，ISGF-3是一种由IFN-α激活的转录复合物。91千道尔顿DNA结合蛋白的IFN-γ依赖性激活需要该蛋白在酪氨酸上进行细胞质磷酸化。响应IFN-α而被磷酸化的113千道尔顿ISGF-3蛋白，在响应IFN-γ时未被磷酸化，也未转位至细胞核。因此，两种不同的配体导致潜在细胞质转录因子不同组合的酪氨酸磷酸化，然后这些转录因子作用于不同的DNA结合位点。
