title: Mice deficient in protein tyrosine phosphatase receptor type Z are resistant to gastric ulcer induction by VacA of Helicobacter pylori.
abstract: The vacuolating cytotoxin VacA produced by Helicobacter pylori causes massive cellular vacuolation in vitro and gastric tissue damage in vivo, leading to gastric ulcers, when administered intragastrically. Here we report that mice deficient in protein tyrosine phosphatase receptor type Z (Ptprz, also called PTP-zeta or RPTP-beta, encoded by Ptprz) do not show mucosal damage by VacA, although VacA is incorporated into the gastric epithelial cells to the same extent as in wild-type mice. Primary cultures of gastric epithelial cells from Ptprz+/+ and Ptprz-/- mice also showed similar incorporation of VacA, cellular vacuolation and reduction in cellular proliferation, but only Ptprz+/+ cells showed marked detachment from a reconstituted basement membrane 24 h after treatment with VacA. VacA bound to Ptprz, and the levels of tyrosine phosphorylation of the G protein-coupled receptor kinase-interactor 1 (Git1), a Ptprz substrate, were higher after treatment with VacA, indicating that VacA behaves as a ligand for Ptprz. Furthermore, pleiotrophin (PTN), an endogenous ligand of Ptprz, also induced gastritis specifically in Ptprz+/+ mice when administered orally. Taken together, these data indicate that erroneous Ptprz signaling induces gastric ulcers.
authors.affiliation: Division of Molecular Neurobiology, National Institute for Basic Biology, 38 Nishigonaka, Myodaiji-cho, Okazaki 444-8585, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Fujikawa
authors.forename: Daisuke
authors.initials: D
authors.lastname: Shirasaka
authors.forename: Shoichi
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Ota
authors.forename: Kinnosuke
authors.initials: K
authors.lastname: Yahiro
authors.forename: Masahide
authors.initials: M
authors.lastname: Fukada
authors.forename: Takafumi
authors.initials: T
authors.lastname: Shintani
authors.forename: Akihiro
authors.initials: A
authors.lastname: Wada
authors.forename: Nobuo
authors.initials: N
authors.lastname: Aoyama
authors.forename: Toshiya
authors.initials: T
authors.lastname: Hirayama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukamachi
authors.forename: Masaharu
authors.initials: M
authors.lastname: Noda
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology* / Q000633:toxicity; D018797:Cell Cycle Proteins; D005260:Female; D020690:GTPase-Activating Proteins / Q000378:metabolism; D005756:Gastritis / Q000209:etiology / Q000473:pathology; D016481:Helicobacter Infections / Q000209:etiology* / Q000473:pathology; D016480:Helicobacter pylori / Q000472:pathogenicity; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010750:Phosphoproteins; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D013276:Stomach Ulcer / Q000209:etiology* / Q000473:pathology; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D018797:Cell Cycle Proteins; D020690:GTPase-Activating Proteins; C120766:Git1 protein, mouse; D010750:Phosphoproteins; C074689:VacA protein, Helicobacter pylori; D017027:Protein Tyrosine Phosphatases