Deregulation of beta-catenin signal by Helicobacter pylori CagA requires the CagA-multimerization sequence.

Deregulation of beta-catenin signal by Helicobacter pylori CagA requires the CagA-multimerization sequence. Research Abstract Details 

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Deregulation of beta-catenin signal by Helicobacter pylori CagA requires the CagA-multimerization sequence. Abstract Text:

Yo Kurashima,Naoko Murata-Kamiya,Kenji Kikuchi,Hideaki Higashi,Takeshi Azuma,Satoshi Kondo,Masanori Hatakeyama,Yo Kurashima,Naoko Murata-Kamiya,Kenji Kikuchi,Hideaki Higashi,Takeshi Azuma,Satoshi Kondo,Masanori Hatakeyama,

Infection with Helicobacter pylori cagA-positive strains causes gastritis and peptic ulceration and is associated with gastric adenocarcinoma. The cagA gene product CagA is delivered into gastric epithelial cells, where it undergoes tyrosine phosphorylation by Src family kinases at the C-terminal EPIYA-repeat region. Tyrosine-phosphorylated CagA specifically binds and activates SHP-2 tyrosine phosphatase, causing cell morphological transformation known as the hummingbird phenotype. CagA also destabilizes the E-cadherin/beta-catenin complex to elicit aberrant activation of the beta-catenin signal that underlies intestinal metaplasia. Here we show that translocalization of membranous beta-catenin and subsequent activation of the beta-catenin signal by CagA requires the EPIYA-repeat region, which is characterized by structural variation between CagA of H. pylori isolated in Western countries (Western CagA) and that of East Asian H. pylori isolates (East Asian CagA), but is independent of CagA tyrosine phosphorylation. Detailed analysis using a series of Western and East Asian CagA mutants revealed that deregulation of beta-catenin requires residues 1009-1086 and residues 908-1012 of ABCCC Western CagA and ABD East Asian CagA, respectively, and is mediated by the 16-amino-acid CagA multimerization sequence that is conserved between the 2 geographically distinct H. pylori CagA species. Our results indicate that aberrant activation of the beta-catenin signal, which promotes precancerous intestinal metaplasia, is an inherent and fundamental CagA activity that is independent of the structural polymorphism of CagA.

Deregulation of beta-catenin signal by Helicobacter pylori CagA requires the CagA-multimerization sequence. Publishing Authors By Initials

Y Kurashima,N Murata-Kamiya,K Kikuchi,H Higashi,T Azuma,S Kondo,M Hatakeyama,Y Kurashima,N Murata-Kamiya,K Kikuchi,H Higashi,T Azuma,S Kondo,M Hatakeyama,

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Deregulation of beta-catenin signal by Helicobacter pylori CagA requires the CagA-multimerization sequence. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: International journal of cancer. Journal internati

VOLUME: 122

Page Numbers: 823-31

Journal Abbreviation: Int. J. Cancer

ISSN: 1097-0215

DAY: 15

MONTH: Feb

YEAR: 2008

Deregulation of beta-catenin signal by Helicobacter pylori CagA requires the CagA-multimerization sequence. Information

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LANGUAGE: eng

NlmUniqueID: 42124

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Grant and Affiliation Information for Deregulation of beta-catenin signal by Helicobacter pylori CagA requires the CagA-multimerization sequence.

AFFILIATION: Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.

Country: United States

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MEDLINETA: Int J Cancer

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