KEGG   PATHWAY: hsa05120
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 disease: bacterial
Pathway map
hsa05120  Epithelial cell signaling in Helicobacter pylori infection
hsa05120

Disease
H00320  Helicobacter pylori infection
Organism
Homo sapiens (human) [GN:hsa]
Gene
101927180  ATP6V1FP2; V-type proton ATPase subunit F-like [KO:K02151]
102  ADAM10; disintegrin and metalloproteinase domain-containing protein 10 isoform 1 preproprotein [KO:K06704] [EC:3.4.24.81]
10312  TCIRG1; V-type proton ATPase 116 kDa subunit a 3 isoform a [KO:K02154]
10392  NOD1; nucleotide-binding oligomerization domain-containing protein 1 isoform 1 [KO:K08727]
1147  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform 1 [KO:K04467] [EC:2.7.11.10]
127124  ATP6V1G3; V-type proton ATPase subunit G 3 isoform a [KO:K02152]
1432  MAPK14; mitogen-activated protein kinase 14 isoform 2 [KO:K04441] [EC:2.7.11.24]
1445  CSK; tyrosine-protein kinase CSK isoform 1 [KO:K05728] [EC:2.7.10.4]
150084  IGSF5; immunoglobulin superfamily member 5 [KO:K06786]
155066  ATP6V0E2; V-type proton ATPase subunit e 2 isoform 1 [KO:K02153]
1839  HBEGF; proheparin-binding EGF-like growth factor precursor [KO:K08523]
1956  EGFR; epidermal growth factor receptor isoform a precursor [KO:K04361] [EC:2.7.10.1]
23545  ATP6V0A2; V-type proton ATPase 116 kDa subunit a 2 [KO:K02154]
245972  ATP6V0D2; V-type proton ATPase subunit d 2 [KO:K02146]
245973  ATP6V1C2; V-type proton ATPase subunit C 2 isoform a [KO:K02148]
28964  GIT1; ARF GTPase-activating protein GIT1 isoform 2 [KO:K05737]
2919  CXCL1; growth-regulated alpha protein precursor [KO:K05505]
2920  CXCL2; C-X-C motif chemokine 2 precursor [KO:K05505]
2921  CXCL3; C-X-C motif chemokine 3 precursor [KO:K05505]
3551  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform 1 [KO:K07209] [EC:2.7.11.10]
3576  CXCL8; interleukin-8 isoform 1 precursor [KO:K10030]
3577  CXCR1; C-X-C chemokine receptor type 1 [KO:K04175]
3579  CXCR2; C-X-C chemokine receptor type 2 [KO:K05050]
3725  JUN; transcription factor Jun [KO:K04448]
4067  LYN; tyrosine-protein kinase Lyn isoform A [KO:K05854] [EC:2.7.10.2]
4233  MET; hepatocyte growth factor receptor isoform b preproprotein [KO:K05099] [EC:2.7.10.1]
4790  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform 2 proprotein [KO:K02580]
4792  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
5058  PAK1; serine/threonine-protein kinase PAK 1 isoform 2 [KO:K04409] [EC:2.7.11.1]
50617  ATP6V0A4; V-type proton ATPase 116 kDa subunit a 4 [KO:K02154]
50848  F11R; junctional adhesion molecule A isoform 1 precursor [KO:K06089]
51382  ATP6V1D; V-type proton ATPase subunit D [KO:K02149]
51606  ATP6V1H; V-type proton ATPase subunit H isoform 1 [KO:K02144]
523  ATP6V1A; V-type proton ATPase catalytic subunit A [KO:K02145] [EC:7.1.2.2]
525  ATP6V1B1; V-type proton ATPase subunit B, kidney isoform [KO:K02147]
526  ATP6V1B2; V-type proton ATPase subunit B, brain isoform [KO:K02147]
527  ATP6V0C; V-type proton ATPase 16 kDa proteolipid subunit c [KO:K02155]
528  ATP6V1C1; V-type proton ATPase subunit C 1 [KO:K02148]
529  ATP6V1E1; V-type proton ATPase subunit E 1 isoform a [KO:K02150]
533  ATP6V0B; V-type proton ATPase 21 kDa proteolipid subunit c'' isoform 1 [KO:K03661]
5335  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform b [KO:K01116] [EC:3.1.4.11]
5336  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
534  ATP6V1G2; V-type proton ATPase subunit G 2 isoform a [KO:K02152]
535  ATP6V0A1; V-type proton ATPase 116 kDa subunit a 1 isoform 1 [KO:K02154]
537  ATP6AP1; V-type proton ATPase subunit S1 precursor [KO:K03662]
5599  MAPK8; mitogen-activated protein kinase 8 isoform alpha2 [KO:K04440] [EC:2.7.11.24]
5600  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
5601  MAPK9; mitogen-activated protein kinase 9 isoform alpha2 [KO:K04440] [EC:2.7.11.24]
5602  MAPK10; mitogen-activated protein kinase 10 isoform 1 [KO:K04440] [EC:2.7.11.24]
5603  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
5781  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform 1 [KO:K07293] [EC:3.1.3.48]
5803  PTPRZ1; receptor-type tyrosine-protein phosphatase zeta isoform 1 precursor [KO:K08114] [EC:3.1.3.48]
58494  JAM2; junctional adhesion molecule B isoform 1 precursor [KO:K06735]
5879  RAC1; ras-related C3 botulinum toxin substrate 1 isoform Rac1 [KO:K04392]
5970  RELA; transcription factor p65 isoform 1 [KO:K04735]
6300  MAPK12; mitogen-activated protein kinase 12 isoform 1 [KO:K04441] [EC:2.7.11.24]
6352  CCL5; C-C motif chemokine 5 isoform 1 precursor [KO:K12499]
6416  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform 1 [KO:K04430] [EC:2.7.12.2]
6714  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
6868  ADAM17; disintegrin and metalloproteinase domain-containing protein 17 isoform 1 preproprotein [KO:K06059] [EC:3.4.24.86]
7082  TJP1; tight junction protein 1 isoform a [KO:K05701]
836  CASP3; caspase-3 isoform a preproprotein [KO:K02187] [EC:3.4.22.56]
83700  JAM3; junctional adhesion molecule C isoform 1 precursor [KO:K06785]
8517  IKBKG; NF-kappa-B essential modulator isoform a [KO:K07210]
8992  ATP6V0E1; V-type proton ATPase subunit e 1 [KO:K02153]
9020  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
90423  ATP6V1E2; V-type proton ATPase subunit E 2 [KO:K02150]
9114  ATP6V0D1; V-type proton ATPase subunit d 1 [KO:K02146]
9296  ATP6V1F; V-type proton ATPase subunit F isoform 1 [KO:K02151]
9550  ATP6V1G1; V-type proton ATPase subunit G 1 [KO:K02152]
998  CDC42; cell division control protein 42 homolog isoform 1 precursor [KO:K04393]
Compound
C00014  Ammonia
C00080  H+
C00086  Urea
C00698  Cl-
C01342  NH4+
G00242  Sialyl Lewis x antigen
G00263  Lewis b antigen
Reference
PMID:14700549
  Authors
Naumann M, Crabtree JE.
  Title
Helicobacter pylori-induced epithelial cell signalling in gastric carcinogenesis.
  Journal
Trends Microbiol 12:29-36 (2004)
DOI:10.1016/j.tim.2003.11.005
Reference
PMID:15694859
  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)
DOI:10.1016/j.mib.2004.12.004
Reference
PMID:11389469
  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)
DOI:10.1038/35073084
Reference
PMID:12197905
  Authors
Gerhard M, Rad R, Prinz C, Naumann M.
  Title
Pathogenesis of Helicobacter pylori infection.
  Journal
Helicobacter 7 Suppl 1:17-23 (2002)
DOI:10.1046/j.1523-5378.7.s1.3.x
Related
pathway
hsa00190  Oxidative phosphorylation
hsa04010  MAPK signaling pathway
hsa04210  Apoptosis
hsa04530  Tight junction
KO pathway
ko05120   

DBGET integrated database retrieval system