Human Gene Set: KEGG_EPITHELIAL_CELL_SIGNALING_IN_HELICOBACTER_PYLORI_INFECTION


Standard name KEGG_EPITHELIAL_CELL_SIGNALING_IN_HELICOBACTER_PYLORI_INFECTION
Systematic name M16848
Brief description Epithelial cell signaling in Helicobacter pylori infection
Full description or abstract Two major virulence factors of H. pylori are the vacuolating cytotoxin (VacA) and the cag type-IV secretion system (T4SS) and its translocated effector protein, cytotoxin-associated antigen A (CagA). VacA binds to lipid rafts and glycosylphosphatidylinositol-anchored proteins (GPI-APs) of the target cell membrane. After insertion into the plasma membrane, VacA channels are endocytosed and eventually reach late endosomal compartments, increasing their permeability to anions with enhancement of the electrogenic vacuolar ATPase (v-ATPase) proton pump. In the presence of weak bases, osmotically active acidotropic ions will accumulate in the endosomes. This leads to water influx and vesicle swelling, an essential step in vacuole formation. In addition, it is reported that the VacA cleavage product binds to the tyrosine phosphatase receptor zeta (Ptprz) on epithelial cells and the induced signaling leads to the phosphorylation of the G protein-coupled receptor kinase-interactor 1 (Git1) and induces ulcerogenesis in mice. The other virulence factor cag T4SS mediates the translocation of the effector protein CagA, which is subsequently phosphorylated by a Src kinase. Phosphorylated CagA interacts with the protein tyrosine phosphatase SHP-2, thus stimulating its phosphatase activity. Activated SHP-2 is able to induce MAPK signalling through Ras/Raf-dependent and -independent mechanisms. Deregulation of this pathway by CagA may lead to abnormal proliferation and movement of gastric epithelial cells.
Collection C2: Curated
      CP: Canonical Pathways
            CP:KEGG_LEGACY: KEGG Legacy Pathways
Source publication  
Exact source hsa05120
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External links http://www.genome.jp/kegg/pathway/hsa/hsa05120.html
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Source species Homo sapiens
Contributed by KEGG (Kyoto Encyclopedia of Genes and Genomes)
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identifier namespace
Human_NCBI_Gene_ID
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