KEGG PATHWAY: hsa05120

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 diseases

Pathway map

hsa05120

Epithelial cell signaling in Helicobacter pylori infection

Module

hsa_M00564

Helicobacter pylori pathogenicity signature, cagA pathogenicity island [PATH:hsa05120]

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 (hepatocyte growth factor receptor) [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 (phosphatidylinositol-specific) [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	IL8; interleukin 8 [KO:K10030]
3577	CXCR1; chemokine (C-X-C motif) receptor 1 [KO:K04175]
3579	CXCR2; chemokine (C-X-C motif) receptor 2 [KO:K05050]
102	ADAM10; ADAM metallopeptidase domain 10 [KO:K06704] [EC:3.4.24.81]
6714	SRC; v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) [KO:K05704] [EC:2.7.10.2]
4067	LYN; v-yes-1 Yamaguchi sarcoma viral related oncogene homolog [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 protein (Cdc42/Rac)-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 [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; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha [KO:K04734]
4790	NFKB1; nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 [KO:K02580]
5970	RELA; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735]
10392	NOD1; nucleotide-binding oligomerization domain containing 1 [KO:K08727]
6352	CCL5; chemokine (C-C motif) ligand 5 [KO:K12499]
5803	PTPRZ1; protein tyrosine phosphatase, receptor-type, Z polypeptide 1 [KO:K08114] [EC:3.1.3.48]
28964	GIT1; G protein-coupled receptor kinase interacting ArfGAP 1 [KO:K05737]
836	CASP3; caspase 3, apoptosis-related cysteine peptidase [KO:K02187] [EC:3.4.22.56]
523	ATP6V1A; ATPase, H+ transporting, lysosomal 70kDa, V1 subunit A [KO:K02145] [EC:3.6.3.14]
525	ATP6V1B1; ATPase, H+ transporting, lysosomal 56/58kDa, V1 subunit B1 [KO:K02147] [EC:3.6.3.14]
526	ATP6V1B2; ATPase, H+ transporting, lysosomal 56/58kDa, V1 subunit B2 [KO:K02147] [EC:3.6.3.14]
245973	ATP6V1C2; ATPase, H+ transporting, lysosomal 42kDa, V1 subunit C2 [KO:K02148] [EC:3.6.3.14]
528	ATP6V1C1; ATPase, H+ transporting, lysosomal 42kDa, V1 subunit C1 [KO:K02148] [EC:3.6.3.14]
51382	ATP6V1D; ATPase, H+ transporting, lysosomal 34kDa, V1 subunit D [KO:K02149] [EC:3.6.3.14]
90423	ATP6V1E2; ATPase, H+ transporting, lysosomal 31kDa, V1 subunit E2 [KO:K02150] [EC:3.6.3.14]
529	ATP6V1E1; ATPase, H+ transporting, lysosomal 31kDa, V1 subunit E1 [KO:K02150] [EC:3.6.3.14]
9296	ATP6V1F; ATPase, H+ transporting, lysosomal 14kDa, V1 subunit F [KO:K02151] [EC:3.6.3.14]
9550	ATP6V1G1; ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G1 [KO:K02152] [EC:3.6.3.14]
127124	ATP6V1G3; ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G3 [KO:K02152] [EC:3.6.3.14]
534	ATP6V1G2; ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G2 [KO:K02152] [EC:3.6.3.14]
8992	ATP6V0E1; ATPase, H+ transporting, lysosomal 9kDa, V0 subunit e1 [KO:K02153] [EC:3.6.3.14]
155066	ATP6V0E2; ATPase, H+ transporting V0 subunit e2 [KO:K02153] [EC:3.6.3.14]
10312	TCIRG1; T-cell, immune regulator 1, ATPase, H+ transporting, lysosomal V0 subunit A3 [KO:K02154] [EC:3.6.3.14]
23545	ATP6V0A2; ATPase, H+ transporting, lysosomal V0 subunit a2 [KO:K02154] [EC:3.6.3.14]
50617	ATP6V0A4; ATPase, H+ transporting, lysosomal V0 subunit a4 [KO:K02154] [EC:3.6.3.14]
535	ATP6V0A1; ATPase, H+ transporting, lysosomal V0 subunit a1 [KO:K02154] [EC:3.6.3.14]
9114	ATP6V0D1; ATPase, H+ transporting, lysosomal 38kDa, V0 subunit d1 [KO:K02146] [EC:3.6.3.14]
245972	ATP6V0D2; ATPase, H+ transporting, lysosomal 38kDa, V0 subunit d2 [KO:K02146] [EC:3.6.3.14]
51606	ATP6V1H; ATPase, H+ transporting, lysosomal 50/57kDa, V1 subunit H [KO:K02144] [EC:3.6.3.14]
537	ATP6AP1; ATPase, H+ transporting, lysosomal accessory protein 1 [KO:K03662] [EC:3.6.3.14]
527	ATP6V0C; ATPase, H+ transporting, lysosomal 16kDa, V0 subunit c [KO:K02155] [EC:3.6.3.14]
533	ATP6V0B; ATPase, H+ transporting, lysosomal 21kDa, V0 subunit b [KO:K03661] [EC:3.6.3.14]
2919	CXCL1; chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha) [KO:K05505]

Compound

C00014	NH3
C00080	H+
C00086	Urea
C00698	Cl-
C01342	NH4+
G00242	sialyl Lewis x antigen
G00263	IV2Fuc,III4Fuc-Lc4-Cer

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)

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)

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)

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)

KO pathway

ko05120

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Ontology (3)   
   KEGG BRITE (3)   
Pathway (1)   
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Disease (1)   
   KEGG DISEASE (1)   
Genome (1)   
   KEGG GENOME (1)   
Gene (68)   
   KEGG GENES (68)   
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