Influence of EPIYA-repeat polymorphism on the phosphorylation-dependent biological activity of Helicobacter pylori CagA

Gastroenterology
Masanori NaitoMasanori Hatakeyama

Abstract

Helicobacter pylori CagA-positive strain is associated with gastric adenocarcinoma. CagA is delivered into gastric epithelial cells, where it undergoes tyrosine phosphorylation at the EPIYA sites by Src family kinases (SFKs). Owing to homologous recombination within the 3'-region of the cagA gene, 4 distinct EPIYA sites, each of which is defined by surrounding sequences, are variably assembled in both number and order among CagA proteins from different clinical H pylori isolates. Tyrosine-phosphorylated CagA specifically binds and deregulates SHP-2 via the Western CagA-specific EPIYA-C or East Asian CagA-specific EPIYA-D site, and C-terminal Src kinase (Csk) via the EPIYA-A or EPIYA-B site. Here we investigated the influence of EPIYA-repeat polymorphism on the CagA activity. A series of EPIYA-repeat variants of CagA were expressed in AGS gastric epithelial cells and the ability of individual CagA to bind SHP-2 or Csk was determined by the sequential immunoprecipitation and immunoblotting method. CagA proteins carrying multiple EPIYA-C or EPIYA-D sites bound and deregulated SHP-2 more strongly than those having a single EPIYA-C or EPIYA-D. Furthermore, the ability of CagA to bind Csk was correlated with the number of EPIYA-A and...Continue Reading

Citations

Jan 15, 2008·Proceedings of the National Academy of Sciences of the United States of America·Naomi OhnishiMasanori Hatakeyama
Aug 5, 2011·The Journal of Biological Chemistry·Lisa NagaseMasanori Hatakeyama
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Jul 10, 2009·International Journal of Cancer. Journal International Du Cancer·Motohiro MiuraMasanori Hatakeyama
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Oct 26, 2007·International Journal of Cancer. Journal International Du Cancer·Yo KurashimaMasanori Hatakeyama
May 22, 2009·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·L A SicinschiB G Schneider
May 16, 2014·The Journal of International Medical Research·Lili WangQuanjiang Dong
Aug 5, 2017·International Journal of Molecular Sciences·Tetsuya TsukamotoXueyuan Cao
Feb 26, 2016·World Journal of Gastrointestinal Pathophysiology·Rong-Guang ZhangShuai-Yin Chen

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