Helicobacter pylori CagA Phosphorylation-Independent Function in Epithelial Proliferation and Inflammation

Masato Suzuki, Hitomi Mimuro, Kotaro Kiga, Makoto Fukumatsu, Nozomi Ishijima, Hanako Morikawa, Shigenori Nagai, Shigeo Koyasu, Robert H. Gilman, Dangeruta Kersulyte, Douglas E. Berg, Chihiro Sasakawa

Research output: Contribution to journalArticlepeer-review

Abstract

CagA, a major virulence factor of Helicobacter pylori (Hp), is delivered into gastric epithelial cells and exists in phosphorylated and nonphosphorylated forms. The biological activity of the phosphorylated form is well established; however, function(s) of the nonphosphorylated form remain elusive. Here, we report that a conserved motif in the C-terminal region of CagA, which is distinct from the EPIYA motifs used for phosphorylation and which we designate CRPIA (conserved repeat responsible for phosphorylation-independent activity), plays pivotal roles in Hp pathogenesis. The CRPIA motif in nonphosphorylated CagA was involved in interacting with activated Met, the hepatocyte growth factor receptor, leading to the sustained activation of phosphatidylinositol 3-kinase/Akt signaling in response to Hp infection. This in turn led to the activation of β-catenin and NF-κB signaling, which promote proliferation and inflammation, respectively. Thus, nonphosphorylated CagA activity contributes to the epithelial proliferative and proinflammatory responses associated with development of chronic gastritis and gastric cancer.

Original languageEnglish (US)
Pages (from-to)23-34
Number of pages12
JournalCell Host and Microbe
Volume5
Issue number1
DOIs
StatePublished - Jan 22 2009
Externally publishedYes

Keywords

  • MICROBIO
  • SIGNALING

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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