KEGG   PATHWAY: hsa05120Help
Entry
hsa05120                    Pathway                                

Name
Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human)
Description
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.
Class
Human Diseases; Infectious diseases
BRITE hierarchy
Pathway map
Epithelial cell signaling in Helicobacter pylori infection
hsa05120

All organismsOrtholog table
Disease
H00320  
Helicobacter pylori infection
Organism
Homo sapiens (human) [GN:hsa]
Gene
5781  
PTPN11; protein tyrosine phosphatase, non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
4233  
MET; MET proto-oncogene, receptor tyrosine kinase [KO:K05099] [EC:2.7.10.1]
5335  
PLCG1; phospholipase C gamma 1 [KO:K01116] [EC:3.1.4.11]
5336  
PLCG2; phospholipase C gamma 2 [KO:K05859] [EC:3.1.4.11]
7082  
TJP1; tight junction protein 1 [KO:K05701]
50848  
F11R; F11 receptor [KO:K06089]
58494  
JAM2; junctional adhesion molecule 2 [KO:K06735]
83700  
JAM3; junctional adhesion molecule 3 [KO:K06785]
150084  
IGSF5; immunoglobulin superfamily member 5 [KO:K06786]
6868  
ADAM17; ADAM metallopeptidase domain 17 [KO:K06059] [EC:3.4.24.86]
1839  
HBEGF; heparin binding EGF like growth factor [KO:K08523]
1956  
EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
3576  
CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030]
3577  
CXCR1; C-X-C motif chemokine receptor 1 [KO:K04175]
3579  
CXCR2; C-X-C motif chemokine receptor 2 [KO:K05050]
102  
ADAM10; ADAM metallopeptidase domain 10 [KO:K06704] [EC:3.4.24.81]
6714  
SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
4067  
LYN; LYN proto-oncogene, Src family tyrosine kinase [KO:K05854] [EC:2.7.10.2]
1445  
CSK; c-src tyrosine kinase [KO:K05728] [EC:2.7.10.2]
5879  
RAC1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
998  
CDC42; cell division cycle 42 [KO:K04393]
5600  
MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
6300  
MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
5603  
MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
1432  
MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
5058  
PAK1; p21 (RAC1) activated kinase 1 [KO:K04409] [EC:2.7.11.1]
6416  
MAP2K4; mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
5599  
MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
5602  
MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
5601  
MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
3725  
JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
9020  
MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
1147  
CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
3551  
IKBKB; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta [KO:K07209] [EC:2.7.11.10]
8517  
IKBKG; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma [KO:K07210]
4792  
NFKBIA; NFKB inhibitor alpha [KO:K04734]
4790  
NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
5970  
RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
10392  
NOD1; nucleotide binding oligomerization domain containing 1 [KO:K08727]
6352  
CCL5; C-C motif chemokine ligand 5 [KO:K12499]
5803  
PTPRZ1; protein tyrosine phosphatase, receptor type Z1 [KO:K08114] [EC:3.1.3.48]
28964  
GIT1; GIT ArfGAP 1 [KO:K05737]
836  
CASP3; caspase 3 [KO:K02187] [EC:3.4.22.56]
523  
ATP6V1A; ATPase H+ transporting V1 subunit A [KO:K02145] [EC:3.6.3.14]
525  
ATP6V1B1; ATPase H+ transporting V1 subunit B1 [KO:K02147]
526  
ATP6V1B2; ATPase H+ transporting V1 subunit B2 [KO:K02147]
245973  
ATP6V1C2; ATPase H+ transporting V1 subunit C2 [KO:K02148]
528  
ATP6V1C1; ATPase H+ transporting V1 subunit C1 [KO:K02148]
51382  
ATP6V1D; ATPase H+ transporting V1 subunit D [KO:K02149]
90423  
ATP6V1E2; ATPase H+ transporting V1 subunit E2 [KO:K02150]
529  
ATP6V1E1; ATPase H+ transporting V1 subunit E1 [KO:K02150]
9296  
ATP6V1F; ATPase H+ transporting V1 subunit F [KO:K02151]
9550  
ATP6V1G1; ATPase H+ transporting V1 subunit G1 [KO:K02152]
127124  
ATP6V1G3; ATPase H+ transporting V1 subunit G3 [KO:K02152]
534  
ATP6V1G2; ATPase H+ transporting V1 subunit G2 [KO:K02152]
8992  
ATP6V0E1; ATPase H+ transporting V0 subunit e1 [KO:K02153]
155066  
ATP6V0E2; ATPase H+ transporting V0 subunit e2 [KO:K02153]
10312  
TCIRG1; T-cell immune regulator 1, ATPase H+ transporting V0 subunit a3 [KO:K02154]
23545  
ATP6V0A2; ATPase H+ transporting V0 subunit a2 [KO:K02154]
50617  
ATP6V0A4; ATPase H+ transporting V0 subunit a4 [KO:K02154]
535  
ATP6V0A1; ATPase H+ transporting V0 subunit a1 [KO:K02154]
9114  
ATP6V0D1; ATPase H+ transporting V0 subunit d1 [KO:K02146]
245972  
ATP6V0D2; ATPase H+ transporting V0 subunit d2 [KO:K02146]
51606  
ATP6V1H; ATPase H+ transporting V1 subunit H [KO:K02144]
537  
ATP6AP1; ATPase H+ transporting accessory protein 1 [KO:K03662]
527  
ATP6V0C; ATPase H+ transporting V0 subunit c [KO:K02155]
533  
ATP6V0B; ATPase H+ transporting V0 subunit b [KO:K03661]
2919  
CXCL1; C-X-C motif chemokine ligand 1 [KO:K05505]
Compound
C00014  
Ammonia
C00080  
H+
C00086  
Urea
C00698  
Cl-
C01342  
NH4+
G00242  
Sialyl Lewis x antigen
G00263  
IV2Fuc,III4Fuc-Lc4-Cer
Reference
  Authors
Naumann M, Crabtree JE.
  Title
Helicobacter pylori-induced epithelial cell signalling in gastric carcinogenesis.
  Journal
Trends Microbiol 12:29-36 (2004)
Reference
  Authors
Rieder G, Fischer W, Haas R.
  Title
Interaction of Helicobacter pylori with host cells: function of secreted and translocated molecules.
  Journal
Curr Opin Microbiol 8:67-73 (2005)
Reference
  Authors
Montecucco C, Rappuoli R.
  Title
Living dangerously: how Helicobacter pylori survives in the human stomach.
  Journal
Nat Rev Mol Cell Biol 2:457-66 (2001)
Reference
  Authors
Gerhard M, Rad R, Prinz C, Naumann M.
  Title
Pathogenesis of Helicobacter pylori infection.
  Journal
Helicobacter 7 Suppl 1:17-23 (2002)
KO pathway
 

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