Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA.
J Cell Biochem. 2012 Aug;113(8):2754-64. doi: 10.1002/jcb.24152.
PKR (protein kinase, RNA activated) is an interferon (IFN)-induced serine-threonine protein kinase and is one of the key mediators in IFN's cellular actions. Although double-stranded (ds) RNA is the most relevant PKR activator during viral infections, PACT acts as a stress-modulated activator of PKR and is an important regulator of PKR dependent signaling pathways in the absence of viral infections. Stress-induced phosphorylation of PACT is essential for PACT's association with PKR leading to PKR activation. PKR activation by PACT leads to phosphorylation of translation initiation factor eIF2α, inhibition of protein synthesis, and apoptosis. In the present study, we have investigated the functional significance of PACT-PACT interaction in mediating PKR activation in response to cellular stress. Our results suggest that enhanced interaction between PACT molecules when PACT is phosphorylated in response to stress signals on serines 246 and 287 is essential for efficient PKR activation. Using a point mutant of PACT that is deficient in PACT-PACT interaction, we demonstrate that PACT-PACT interaction is essential for efficient PKR activation.
PKR（蛋白激酶，RNA 激活）是一种干扰素（IFN）诱导的丝氨酸-苏氨酸蛋白激酶，是 IFN 细胞作用的关键介质之一。虽然双链（ds）RNA 是病毒感染期间最相关的 PKR 激活剂，但 PACT 作为应激调节的 PKR 激活剂，在没有病毒感染的情况下，是 PKR 依赖性信号通路的重要调节剂。应激诱导的 PACT 磷酸化对于 PACT 与 PKR 的结合导致 PKR 激活至关重要。PACT 激活 PKR 导致翻译起始因子 eIF2α 的磷酸化、蛋白质合成的抑制和细胞凋亡。在本研究中，我们研究了 PACT-PACT 相互作用在介导细胞应激反应中 PKR 激活的功能意义。我们的结果表明，当 PACT 响应于丝氨酸 246 和 287 上的应激信号而被磷酸化时，PACT 分子之间增强的相互作用对于有效的 PKR 激活是必需的。使用 PACT 的点突变体，该突变体缺乏 PACT-PACT 相互作用，我们证明 PACT-PACT 相互作用对于有效的 PKR 激活是必需的。
