Gupta S, Campbell D, Dérijard B, Davis R J
Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester 01605.
Science. 1995 Jan 20;267(5196):389-93. doi: 10.1126/science.7824938.
Treatment of cells with pro-inflammatory cytokines or ultraviolet radiation causes activation of the c-Jun NH2-terminal protein kinase (JNK). Activating transcription factor-2 (ATF2) was found to be a target of the JNK signal transduction pathway. ATF2 was phosphorylated by JNK on two closely spaced threonine residues within the NH2-terminal activation domain. The replacement of these phosphorylation sites with alanine inhibited the transcriptional activity of ATF2. These mutations also inhibited ATF2-stimulated gene expression mediated by the retinoblastoma (Rb) tumor suppressor and the adenovirus early region 1A (E1A) oncoprotein. Furthermore, expression of dominant-negative JNK inhibited ATF2 transcriptional activity. Together, these data demonstrate a role for the JNK signal transduction pathway in transcriptional responses mediated by ATF2.
用促炎细胞因子或紫外线辐射处理细胞会导致c-Jun氨基末端蛋白激酶（JNK）激活。发现激活转录因子2（ATF2）是JNK信号转导途径的一个靶点。ATF2在氨基末端激活域内两个紧密相邻的苏氨酸残基上被JNK磷酸化。用丙氨酸取代这些磷酸化位点会抑制ATF2的转录活性。这些突变也抑制了由视网膜母细胞瘤（Rb）肿瘤抑制因子和腺病毒早期区域1A（E1A）癌蛋白介导的ATF2刺激的基因表达。此外，显性负性JNK的表达抑制了ATF2的转录活性。总之，这些数据证明了JNK信号转导途径在由ATF2介导的转录反应中的作用。
