KEGG   PATHWAY: hpy05120
hpy05120                    Pathway                                

Epithelial cell signaling in Helicobacter pylori infection - Helicobacter pylori 26695
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.
Human Diseases; Infectious disease: bacterial
Pathway map
hpy05120  Epithelial cell signaling in Helicobacter pylori infection

hpy_M00564  Helicobacter pylori pathogenicity signature, cagA pathogenicity island [PATH:hpy05120]
Helicobacter pylori 26695 [GN:hpy]
HP0547  cytotoxicity-associated immunodominant antigen [KO:K15842]
HP0520  cag pathogenicity island protein cag1 [KO:K12086]
HP0522  cag pathogenicity island protein cag3 [KO:K12088]
HP0523  cag pathogenicity island protein cag4 [KO:K12089]
HP0524  type IV secretion system protein [KO:K12090]
HP1421  type IV secretion system ATPase [KO:K03196] [EC:]
HP0525  type IV secretion system ATPase [KO:K03196] [EC:]
HP0526  Cag-specific translocation protein CagZ [KO:K12091]
HP0527  cag pathogenicity island protein cag7 [KO:K12092]
HP0528  cag pathogenicity island protein cag8 [KO:K12093]
HP0529  cag pathogenicity island protein cag9 [KO:K12094]
HP0530  type IV secretion system protein [KO:K12095]
HP0531  cag pathogenicity island protein cag11 [KO:K12096]
HP0532  cag pathogenicity island protein cag12 [KO:K12097]
HP0534  cag pathogenicity island protein cag13 [KO:K12098]
HP0535  cag pathogenicity island protein cag14 [KO:K12099]
HP0536  cag pathogenicity island protein cag15 [KO:K12100]
HP0537  cag pathogenicity island protein cag16 [KO:K12101]
HP0538  cag pathogenicity island protein cag17 [KO:K12102]
HP0539  cag pathogenicity island protein cag18 [KO:K12103]
HP0540  cag pathogenicity island protein cag19 [KO:K12104]
HP0541  cag pathogenicity island protein cag20 [KO:K12105]
HP0542  cag pathogenicity island protein cag21 [KO:K12106]
HP0543  cag pathogenicity island protein cag22 [KO:K12107]
HP0544  type IV secretion/conjugal transfer ATPase [KO:K12108] [EC:]
HP0545  cag pathogenicity island protein cag24 [KO:K12109]
HP0546  cag pathogenicity island protein cag25 [KO:K12110]
HP0887  vacuolating cytotoxin autotransporter [KO:K11028]
HP0071  ureI; acid-activated urea channel [KO:K03191]
HP0073  urease subunit alpha [KO:K14048] [EC:]
HP0072  ureB; urease subunit beta [KO:K01428] [EC:]
HP0169  protease [KO:K08303] [EC:3.4.-.-]
HP0912  membrane protein [KO:K15843]
HP0913  membrane protein [KO:K15844]
HP0009  membrane protein [KO:K15845]
HP0797  neuraminyllactose-binding hemagglutinin [KO:K15846]
HP0492  neuraminyllactose-binding hemagglutinin [KO:K15846]
HP0410  neuraminyllactose-binding hemagglutinin HpaA [KO:K15846]
HP1243  membrane protein [KO:K15847]
HP0725  omp17; membrane protein [KO:K15848]
C00014  Ammonia
C00080  H+
C00086  Urea
C00698  Cl-
C01342  NH4+
G00242  Sialyl Lewis x antigen
G00263  IV2Fuc,III4Fuc-Lc4-Cer
Naumann M, Crabtree JE.
Helicobacter pylori-induced epithelial cell signalling in gastric carcinogenesis.
Trends Microbiol 12:29-36 (2004)
Rieder G, Fischer W, Haas R.
Interaction of Helicobacter pylori with host cells: function of secreted and translocated molecules.
Curr Opin Microbiol 8:67-73 (2005)
Montecucco C, Rappuoli R.
Living dangerously: how Helicobacter pylori survives in the human stomach.
Nat Rev Mol Cell Biol 2:457-66 (2001)
Gerhard M, Rad R, Prinz C, Naumann M.
Pathogenesis of Helicobacter pylori infection.
Helicobacter 7 Suppl 1:17-23 (2002)
hpy00190  Oxidative phosphorylation
hpy03070  Bacterial secretion system
KO pathway

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