title: New Insights into VacA Intoxication Mediated through Its Cell Surface Receptors.
abstract: Helicobacter pylori (H. pylori), a major cause of gastroduodenal diseases, produces VacA, a vacuolating cytotoxin associated with gastric inflammation and ulceration. The C-terminal domain of VacA plays a crucial role in receptor recognition on target cells. We have previously identified three proteins (i.e., RPTPα, RPTPβ, and LRP1) that serve as VacA receptors. These receptors contribute to the internalization of VacA into epithelial cells, activate signal transduction pathways, and contribute to cell death and gastric ulceration. In addition, other factors (e.g., CD18, sphingomyelin) have also been identified as cell-surface, VacA-binding proteins. Since we believe that, following interactions with its host cell receptors, VacA participates in events leading to disease, a better understanding of the cellular function of VacA receptors may provide valuable information regarding the mechanisms underlying the pleiotropic actions of VacA and the pathogenesis of H. pylori-mediated disease. In this review, we focus on VacA receptors and their role in events leading to cell damage.
authors.affiliation: Department of Molecular Infectiology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan. yahirok@faculty.chiba-u.jp.
authors.forename: Kinnosuke
authors.initials: K
authors.lastname: Yahiro
authors.affiliation: Department of Bacteriology, Institute of Tropical Medicine, Nagasaki University, 1-12-4, Sakamoto, Nagasaki 852-8523, Japan. hirayama@nagasaki-u.ac.jp.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Hirayama
authors.affiliation: Cardiovascular and Pulmonary Branch, NHLBI, NIH, Building 10, Room 6D03, MSC 1590, Bethesda, MD 20892-1590, USA. mossj@nhlbi.nih.gov.
authors.forename: Joel
authors.initials: J
authors.lastname: Moss
authors.affiliation: Department of Molecular Infectiology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan. noda@faculty.chiba-u.jp.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Noda
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000633:toxicity*; D006801:Humans; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D011956:Receptors, Cell Surface; C074689:VacA protein, Helicobacter pylori
keywords: RPTPβ; low-density lipoprotein receptor-related protein-1 (LRP1); receptor-like protein tyrosine phosphatase (RPTP) α; receptors; vacuolating cytotoxin (VacA)