HUSCAP logo Hokkaido Univ. logo

Hokkaido University Collection of Scholarly and Academic Papers >
Institute for Genetic Medicine >
Peer-reviewed Journal Articles, etc >

Focal Adhesion Kinase Is a Substrate and Downstream Effector of SHP-2 Complexed with Helicobacter pylori CagA

Files in This Item:
MCB26_1.pdf18.48 MBPDFView/Open
Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/5960

Title: Focal Adhesion Kinase Is a Substrate and Downstream Effector of SHP-2 Complexed with Helicobacter pylori CagA
Authors: Tsutsumi, Ryouhei Browse this author
Takahashi, Atsushi Browse this author
Azuma, Takeshi Browse this author
Higashi, Hideaki Browse this author →KAKEN DB
Hatakeyama, Masanori5 Browse this author →KAKEN DB
Authors(alt): 畠山, 昌則5
Issue Date: Jan-2006
Publisher: American Society for Microbiology
Journal Title: Molecular and Cellular Biology
Volume: 26
Issue: 1
Start Page: 261
End Page: 276
Publisher DOI: 10.1128/MCB.26.1.261-276.2006
Abstract: Infection with cagA-positive Helicobacter pylori (H. pylori) is associated with atrophic gastritis, peptic ulcer, and gastric adenocarcinoma. The cagA gene product CagA is translocated from H. pylori into gastric epithelial cells and undergoes tyrosine phosphorylation by Src family kinases (SFKs). Tyrosine-phosphorylated CagA binds and activates SHP-2 phosphatase and the C-terminal Src kinase (Csk) while inducing an elongated cell shape termed the "hummingbird phenotype." Here we show that CagA reduces the level of focal adhesion kinase (FAK) tyrosine phosphorylation in gastric epithelial cells. The decrease in phosphorylated FAK is due to SHP-2-mediated dephosphorylation of FAK at the activating phosphorylation sites, not due to Csk-dependent inhibition of SFKs, which phosphorylate FAK. Coexpression of constitutively active FAK with CagA inhibits induction of the hummingbird phenotype, whereas expression of dominant-negative FAK elicits an elongated cell shape characteristic of the hummingbird phenotype. These results indicate that inhibition of FAK by SHP-2 plays a crucial role in the morphogenetic activity of CagA. Impaired cell adhesion and increased motility by CagA may be involved in the development of gastric lesions associated with cagA-positive H. pylori infection
Rights: Copyright © American Society for Microbiology
Type: article (author version)
URI: http://hdl.handle.net/2115/5960
Appears in Collections:遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 畠山 昌則

Export metadata:

OAI-PMH ( junii2 , jpcoar )

MathJax is now OFF:


 

Feedback - Hokkaido University