Su Qiaozhu, Wang Shuo, Baltzis Dionissios, Qu Li-Ke, Raven Jennifer F, Li Suiyang, Wong Andrew Hoi-Tao, Koromilas Antonis E
Lady Davis Institute, Sir Mortimer B. Davis-Jewish General Hospital, 3999 Cote Ste-Catherine Road, Montreal, Quebec, Canada.
EMBO Rep. 2007 Mar;8(3):265-70. doi: 10.1038/sj.embor.7400891. Epub 2007 Feb 9.
The interferon (IFN)-inducible, double-stranded RNA activated protein kinase (PKR) is a dual-specificity kinase, which has an essential role in the regulation of protein synthesis by phosphorylating the translation eukaryotic initiation factor 2 (eIF2). Here, we show the tyrosine (Tyr) phosphorylation of PKR in response to type I or type II IFNs. We show that PKR physically interacts with either Jak1 or Tyk2 in unstimulated cells and that these interactions are increased in IFN-treated cells. We also show that PKR acts as a substrate of activated Jaks, and is phosphorylated at Tyr 101 and Tyr 293 both in vitro and in vivo. Moreover, we provide strong evidence that both the induction of eIF2alpha phosphorylation and inhibition of protein synthesis by IFN are impaired in cells lacking Jak1 or Tyk2, which corresponds to a lack of induction of PKR tyrosine phosphorylation. We conclude that PKR tyrosine phosphorylation provides an important link between IFN signalling and translational control through the regulation of eIF2alpha phosphorylation.
干扰素（IFN）诱导的双链RNA激活蛋白激酶（PKR）是一种双特异性激酶，它通过磷酸化翻译真核起始因子2（eIF2）在蛋白质合成调控中起重要作用。在此，我们展示了PKR对I型或II型IFN的酪氨酸（Tyr）磷酸化反应。我们发现，在未受刺激的细胞中，PKR与Jak1或Tyk2发生物理相互作用，且这些相互作用在IFN处理的细胞中增强。我们还表明，PKR作为活化Jaks的底物，在体外和体内的Tyr 101和Tyr 293位点均被磷酸化。此外，我们提供了有力证据，在缺乏Jak1或Tyk2的细胞中，IFN诱导的eIF2α磷酸化和蛋白质合成抑制均受损，这与PKR酪氨酸磷酸化的诱导缺失相对应。我们得出结论，PKR酪氨酸磷酸化通过调节eIF2α磷酸化在IFN信号传导和翻译控制之间提供了重要联系。
