Welsh G I, Miyamoto S, Price N T, Safer B, Proud C G
Department of Biochemistry, School of Medical Sciences, University of Bristol, United Kingdom.
J Biol Chem. 1996 May 10;271(19):11410-3. doi: 10.1074/jbc.271.19.11410.
Mitogenic stimulation of T-lymphocytes causes a rapid activation or protein synthesis, which reflects in part increased expression of many translation components. Their levels, however, rise more slowly than the rate of protein synthesis, indicating an enhancement of the efficiency of their utilization. Initiation factor eIF2B catalyzes a key regulatory step in the initiation of translation, and we have therefore studied its activity following T-cell activation. eIF2B activity rises quickly, increasing as early as 5 min after cell stimulation. This initial phase is followed by an additional slow but substantial increase in eIF2B activity. The level of eIF2B subunits did not change over the initial rapid phase but did increase at later time points. Northern analysis revealed that levels of eIF2B mRNA only rose during the later phase. The rapid activation of EIF2B following mitogenic stimulation of T-cells is therefore mediated by factors other than its own concentration. The largest (epsilon) subunit of eIF2B is a substrate for glycogen synthase kinase-3 (GSK-3), the activity of which rapidly decreases following T-cell activation. Since phosphorylation of eIF2B by GSK-3 appears to inhibit nucleotide exchange in vitro, this provides a potential mechanism by which eIF2B may be activated.
T淋巴细胞的有丝分裂原刺激会导致快速的激活或蛋白质合成，这部分反映了许多翻译成分表达的增加。然而，它们的水平上升速度比蛋白质合成速度慢，这表明其利用效率提高。起始因子eIF2B催化翻译起始中的一个关键调节步骤，因此我们研究了T细胞激活后它的活性。eIF2B活性迅速上升，早在细胞刺激后5分钟就开始增加。在这个初始阶段之后，eIF2B活性会有额外的缓慢但显著的增加。eIF2B亚基的水平在最初的快速阶段没有变化，但在随后的时间点确实增加了。Northern分析显示，eIF2B mRNA水平仅在后期上升。因此，T细胞有丝分裂原刺激后EIF2B的快速激活是由其自身浓度以外的因素介导的。eIF2B最大的（ε）亚基是糖原合酶激酶-3（GSK-3）的底物，T细胞激活后其活性迅速降低。由于GSK-3对eIF2B的磷酸化在体外似乎会抑制核苷酸交换，这提供了一种eIF2B可能被激活的潜在机制。
