Helicobacter pylori CagA Phosphorylation-Independent Function in Epithelial Proliferation and Inflammation
| Autor: | Dangeruta Kersulyte, Hanako Morikawa, Makoto Fukumatsu, Shigeo Koyasu, Robert H. Gilman, Douglas E. Berg, Nozomi Ishijima, Hitomi Mimuro, Shigenori Nagai, Chihiro Sasakawa, Masato Suzuki, Kotaro Kiga |
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| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
MICROBIO Epithelium Mice Phosphatidylinositol 3-Kinases chemistry.chemical_compound 0302 clinical medicine Protein Interaction Mapping Phosphorylation beta Catenin Mice Inbred BALB C 0303 health sciences NF-kappa B Proto-Oncogene Proteins c-met 3. Good health Oncogene Protein v-akt SIGNALING 030220 oncology & carcinogenesis Signal transduction Protein Binding Signal Transduction Virulence Factors Molecular Sequence Data Biology Microbiology Cell Line Proinflammatory cytokine 03 medical and health sciences Bacterial Proteins Proto-Oncogene Proteins Immunology and Microbiology(all) Virology Animals Humans CagA Receptors Growth Factor Amino Acid Sequence Phosphatidylinositol Molecular Biology Protein kinase B Cell Proliferation 030304 developmental biology Inflammation Antigens Bacterial Helicobacter pylori biology.organism_classification chemistry Hepatocyte Growth Factor Receptor Immunology Cancer research bacteria Parasitology Sequence Alignment |
| Zdroj: | Cell Host & Microbe. 5:23-34 |
| ISSN: | 1931-3128 |
| Popis: | SummaryCagA, a major virulence factor of Helicobacter pylori (Hp), is delivered into gastric epithelial cells and exists in phosphorylated and nonphosphorylated forms. The biological activity of the phosphorylated form is well established; however, function(s) of the nonphosphorylated form remain elusive. Here, we report that a conserved motif in the C-terminal region of CagA, which is distinct from the EPIYA motifs used for phosphorylation and which we designate CRPIA (conserved repeat responsible for phosphorylation-independent activity), plays pivotal roles in Hp pathogenesis. The CRPIA motif in nonphosphorylated CagA was involved in interacting with activated Met, the hepatocyte growth factor receptor, leading to the sustained activation of phosphatidylinositol 3-kinase/Akt signaling in response to Hp infection. This in turn led to the activation of β-catenin and NF-κB signaling, which promote proliferation and inflammation, respectively. Thus, nonphosphorylated CagA activity contributes to the epithelial proliferative and proinflammatory responses associated with development of chronic gastritis and gastric cancer. |
| Databáze: | OpenAIRE |
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