Journal
NATURE GENETICS
Volume 33, Issue 3, Pages 375-381Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng1112
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The vacuolating cytotoxin VacA produced by Helicobacter pylori causes massive cellular vacuolation in vitro(1-3) and gastric tissue damage in vivo, leading to gastric ulcers, when administered intragastrically(4). Here we report that mice deficient in protein tyrosine phosphatase receptor type Z (Ptprz, also called PTP-xi 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.
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