Bleiblo Farag, Michael Paul, Brabant Danielle, Ramana Chilakamarti V, Tai Tc, Saleh Mazen, Parrillo Joseph E, Kumar Anand, Kumar Aseem
Department of Chemistry and Biochemistry and the Biomolecular Sciences Programme, Laurentian University Sudbury, ON, Canada, P3E 2C6 ; Department of Biology, University of Benghazi Benghazi, Libya.
Int J Clin Exp Med. 2013;6(1):16-25. Epub 2012 Nov 18.
Discriminating the molecular patterns associated with RNA is central to innate immunity. The protein kinase PKR is a cytosolic sensor involved in the recognition of viral dsRNA and triggering interferon-induced signaling. Here, we identified bacterial RNA as a novel distinct pattern recognized by PKR. We show that the tyrosine phosphorylation of PKR induced by either bacterial RNA or poly I:C is impaired in mutant cells lacking TYK2, JAK1, or JAK2 kinases. PKR was found to be a direct substrate for the activated JAKs. Our results indicated that the double-stranded structures of bacterial RNA are required to fully activate PKR. These results suggest that bacterial RNA signaling is analogous in some respects to that of viral RNA and interferons and may have implications in bacterial immunity.
区分与RNA相关的分子模式是先天免疫的核心。蛋白激酶PKR是一种胞质传感器,参与病毒双链RNA的识别并触发干扰素诱导的信号传导。在此,我们将细菌RNA鉴定为PKR识别的一种新型独特模式。我们发现,在缺乏TYK2、JAK1或JAK2激酶的突变细胞中,细菌RNA或聚肌胞苷酸(poly I:C)诱导的PKR酪氨酸磷酸化受损。PKR被发现是活化JAKs的直接底物。我们的结果表明,细菌RNA的双链结构是充分激活PKR所必需的。这些结果表明,细菌RNA信号传导在某些方面类似于病毒RNA和干扰素的信号传导,可能对细菌免疫有影响。