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

• Published in: Proceedings of the National Academy of Sciences - PNAS 2010-12, Vol.107 (50), p.21418-21423
• Main Authors: Kim, Do Jin, Park, Kang-Seo, Kim, Jung-Ho, Yang, Sang-Hwa, Yoon, Ji Young, Han, Byeong-Gu, Kim, Hyoun Sook, Lee, Sang Jae, Jang, Jun Young, Kim, Kyoung Hoon, Kim, Mi Jung, Song, Jin-Su, Kim, Hie-Joon, Park, Chung-Mo, Lee, Sang-Kyou, Lee, Byung Il, Suh, Se Won
• Format: Article
• Language: English
• Subjects: Adenosine Diphosphate - metabolism; Adenosine Triphosphate - analogs & derivatives; Adenosine Triphosphate - metabolism; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Catalytic Domain; Cell Line, Tumor; Helicobacter pylori - enzymology; Helicobacter pylori - genetics; Helicobacter pylori - pathogenicity; Humans; Inflammation - metabolism; Inflammation - microbiology; Models, Molecular; NF-kappa B - genetics; NF-kappa B - metabolism; Phosphorylation; Protein Structure, Tertiary; Protein-Serine-Threonine Kinases - chemistry; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Virulence Factors - chemistry; Virulence Factors - genetics; Virulence Factors - metabolism
• ISSN: 1091-6490
• DOI: 10.1073/pnas.1010153107

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).