Helicobacter pylori proinflammatory protein up-regulates NF-κB as a cell-translocating Ser/Thr kinase

被引:49
作者
Kim, Do Jin [2 ]
Park, Kang-Seo [3 ]
Kim, Jung-Ho [1 ]
Yang, Sang-Hwa [1 ]
Yoon, Ji Young [2 ]
Han, Byeong-Gu [4 ]
Kim, Hyoun Sook [2 ]
Lee, Sang Jae [2 ]
Jang, Jun Young [2 ]
Kim, Kyoung Hoon [2 ]
Kim, Mi Jung [2 ]
Song, Jin-Su [2 ]
Kim, Hie-Joon [2 ]
Park, Chung-Mo [2 ]
Lee, Sang-Kyou [1 ]
Lee, Byung Il [4 ]
Suh, Se Won [2 ,5 ]
机构
[1] Yonsei Univ, Natl Creat Res Initiat Ctr Inflammatory Response, Coll Life Sci & Biotechnol, Dept Biotechnol, Seoul 120749, South Korea
[2] Seoul Natl Univ, Coll Nat Sci, Dept Chem, Seoul 151747, South Korea
[3] Kyung Hee Univ, Grad Sch, Dept Biomed Sci, Seoul 130701, South Korea
[4] Natl Canc Ctr, Res Inst, Div Canc Biol, Canc Cell & Mol Biol Branch, Goyang 410769, Gyeonggi, South Korea
[5] Seoul Natl Univ, Coll Nat Sci, Dept Biophys & Chem Biol, Seoul 151747, South Korea
基金
新加坡国家研究基金会;
关键词
PLASTICITY REGION; TRANSCRIPTIONAL ACTIVITY; PHOSPHORYLATION; MECHANISMS; SUBUNIT; ACTIVATION; EXPRESSION; SECRETION; INFECTION; GASTRITIS;
D O I
10.1073/pnas.1010153107
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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-kappa B 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-kappa B 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).
引用
收藏
页码:21418 / 21423
页数:6
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