Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea.
Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21418-23. doi: 10.1073/pnas.1010153107. Epub 2010 Nov 22.
There has been considerable interest in virulence genes in the plasticity region of Helicobacter pylori, but little is known about many of these genes. JHP940, one of the virulence factors encoded by the plasticity region of H. pylori strain J99, is a proinflammatory protein that induces tumor necrosis factor-alpha and interleukin-8 secretion as well as enhanced translocation of NF-κB in cultured macrophages. Here we have characterized the structure and function of JHP940 to provide the framework for better understanding its role in inflammation by H. pylori. Our work demonstrates that JHP940 is the first example of a eukaryotic-type Ser/Thr kinase from H. pylori. We show that JHP940 is catalytically active as a protein kinase and translocates into cultured human cells. Furthermore, the kinase activity is indispensable for indirectly up-regulating phosphorylation of NF-κB p65 at Ser276. Our results, taken together, contribute significantly to understanding the molecular basis of the role of JHP940 in inflammation and subsequent pathogenesis caused by H. pylori. We propose to rename the jhp940 gene as ctkA (cell translocating kinase A).
幽门螺杆菌可塑性区域的毒力基因一直备受关注，但对其中许多基因的了解甚少。JHP940 是 J99 株幽门螺杆菌可塑性区域编码的一种毒力因子，是一种促炎蛋白，可诱导肿瘤坏死因子-α和白细胞介素-8 的分泌，并增强培养的巨噬细胞中 NF-κB 的易位。在这里，我们对 JHP940 的结构和功能进行了表征，为更好地了解其在幽门螺杆菌引起的炎症中的作用提供了框架。我们的工作表明，JHP940 是来自幽门螺杆菌的第一个真核型丝氨酸/苏氨酸激酶的例子。我们表明 JHP940 作为蛋白激酶具有催化活性，并易位到培养的人细胞中。此外，激酶活性对于间接上调 NF-κB p65 在 Ser276 的磷酸化是必不可少的。我们的结果共同为理解 JHP940 在炎症中的作用以及随后由幽门螺杆菌引起的发病机制的分子基础做出了重要贡献。我们建议将 jhp940 基因重新命名为 ctkA（细胞易位激酶 A）。
