Helicobacter pylori CagA targets PAR1/MARK kinase to disrupt epithelial cell polarity

Iraj Saadat, Hideaki Higashi, Chikashi Obuse, Mayumi Umeda, Naoko Murata-Kamiya, Yasuhiro Saito, Huaisheng Lu, Naomi Ohnishi, Takeshi Azuma, Atsushi Suzuki, Shigeo Ohno and Masanori Hatakeyama ()
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Iraj Saadat: Graduate School of Science, Hokkaido University, Sapporo 060-0815, Japan
Hideaki Higashi: Graduate School of Science, Hokkaido University, Sapporo 060-0815, Japan
Chikashi Obuse: Hokkaido University, Graduate School of Life Science, Sapporo 001-0021, Japan
Mayumi Umeda: Graduate School of Science, Hokkaido University, Sapporo 060-0815, Japan
Naoko Murata-Kamiya: Graduate School of Science, Hokkaido University, Sapporo 060-0815, Japan
Yasuhiro Saito: Graduate School of Science, Hokkaido University, Sapporo 060-0815, Japan
Huaisheng Lu: Graduate School of Science, Hokkaido University, Sapporo 060-0815, Japan
Naomi Ohnishi: Graduate School of Science, Hokkaido University, Sapporo 060-0815, Japan
Takeshi Azuma: Internal Center for Medical Research and Treatment, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
Atsushi Suzuki: Yokohama City University Graduate School of Medical Science, Yokohama 236-0004, Japan
Shigeo Ohno: Yokohama City University Graduate School of Medical Science, Yokohama 236-0004, Japan
Masanori Hatakeyama: Graduate School of Science, Hokkaido University, Sapporo 060-0815, Japan

Nature, 2007, vol. 447, issue 7142, 330-333

Abstract: H. pylori beats PAR Helicobacter pylori infects more than half of the world's population, and though usually well tolerated, it can cause gastric mucosal damage, peptic ulcers, gastritis and adenocarcinoma. CagA is the main virulence factor of H. pylori, delivered directly by the bacterium into epithelial cells where it interferes with cell signalling. CagA is now shown to bind to the polarity protein, Par-1, inhibiting its phosphorylation and disrupting epithelial cell polarity. This study provides the first molecular link between a human pathogen and the PAR cell polarity machinery, and points to a possible general role for PAR1 inhibition in gastrointestinal carcinogenesis.

Date: 2007
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DOI: 10.1038/nature05765

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