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

Do Jin Kim, Kang Seo Park, Jung Ho Kim, Sang Hwa Yang, Ji Young Yoon, Byeong Gu Han, Hyoun Sook Kim, Sang Jae Lee, Jun Young Jang, Kyoung Hoon Kim, Mi Jung Kim, Jin Su Song, Hie Joon Kim, Chung Mo Park, Sang Kyou Lee, Byung Il Lee, Se Won Suh

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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).

Original languageEnglish
Pages (from-to)21418-21423
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number50
DOIs
Publication statusPublished - 2010 Dec 14

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Helicobacter pylori
Phosphotransferases
Up-Regulation
Proteins
Genes
Inflammation
Virulence Factors
Interleukin-8
Protein Kinases
Virulence
Cultured Cells
Tumor Necrosis Factor-alpha
Macrophages
Phosphorylation

All Science Journal Classification (ASJC) codes

  • General

Cite this

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 ; Il Lee, Byung ; Suh, Se Won. / Helicobacter pylori proinflammatory protein upregulates NF-κB as a cell-translocating Ser/Thr kinase. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 50. pp. 21418-21423.
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title = "Helicobacter pylori proinflammatory protein upregulates NF-κB as a cell-translocating Ser/Thr kinase",
abstract = "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).",
author = "Kim, {Do Jin} and Park, {Kang Seo} and Kim, {Jung Ho} and Yang, {Sang Hwa} and Yoon, {Ji Young} and Han, {Byeong Gu} and Kim, {Hyoun Sook} and Lee, {Sang Jae} and Jang, {Jun Young} and Kim, {Kyoung Hoon} and Kim, {Mi Jung} and Song, {Jin Su} and Kim, {Hie Joon} and Park, {Chung Mo} and Lee, {Sang Kyou} and {Il Lee}, Byung and Suh, {Se Won}",
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Kim, DJ, Park, KS, Kim, JH, Yang, SH, Yoon, JY, Han, BG, Kim, HS, Lee, SJ, Jang, JY, Kim, KH, Kim, MJ, Song, JS, Kim, HJ, Park, CM, Lee, SK, Il Lee, B & Suh, SW 2010, 'Helicobacter pylori proinflammatory protein upregulates NF-κB as a cell-translocating Ser/Thr kinase', Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 50, pp. 21418-21423. https://doi.org/10.1073/pnas.1010153107

Helicobacter pylori proinflammatory protein upregulates NF-κB as a cell-translocating Ser/Thr kinase. / 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; Il Lee, Byung; Suh, Se Won.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 50, 14.12.2010, p. 21418-21423.

Research output: Contribution to journalArticle

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T1 - Helicobacter pylori proinflammatory protein upregulates NF-κB as a cell-translocating Ser/Thr kinase

AU - Kim, Do Jin

AU - Park, Kang Seo

AU - Kim, Jung Ho

AU - Yang, Sang Hwa

AU - Yoon, Ji Young

AU - Han, Byeong Gu

AU - Kim, Hyoun Sook

AU - Lee, Sang Jae

AU - Jang, Jun Young

AU - Kim, Kyoung Hoon

AU - Kim, Mi Jung

AU - Song, Jin Su

AU - Kim, Hie Joon

AU - Park, Chung Mo

AU - Lee, Sang Kyou

AU - Il Lee, Byung

AU - Suh, Se Won

PY - 2010/12/14

Y1 - 2010/12/14

N2 - 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).

AB - 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).

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U2 - 10.1073/pnas.1010153107

DO - 10.1073/pnas.1010153107

M3 - Article

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