Protein tyrosine phosphatase beta, a receptor for Helicobacter pylori vacA toxin.
Helicobacter pylori is the leading bacterial cause of food-borne illness worldwide and plays a major role in the development of chronic gastritis, peptic ulcer, and gastric cancer. Strains isolated from patients contain the cagA gene (cytotoxin-associated gene A) and produce the vacuolating cytotoxin VacA. VacA binding to specific high-affinity cell surface receptors was shown by using indirect immunofluorescence and flow cytometry; high-affinity toxin binding was necessary for cell intoxication. A 250-kDa receptor protein tyrosine phosphatase (RPTP) beta served as a receptor for VacA on AZ-521 cells. The overexpression of RPTP beta conferred VacA sensitivity on BHK-21 cells transfected with the RPTP beta cDNA, consistent with RPTP gamma acting as a receptor for VacA. Increased binding of acid- or alkali-activated VacA to RPTP gamma may alter its activity and possibly accelerate or inhibit dephosphorylation of tyrosine on cytosolic proteins. Understanding the pathological responses of wild type and RPTP gamma-deficient animal models may well provide valuable information regarding the mechanism of VacA toxicity.
Hirayama
Toshiya
T
Department of Bacteriology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan. hirayama@net.nagasaki-u.ac.jp
D000818:Animals; D017209:Apoptosis; D001426:Bacterial Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000382:microbiology; D003603:Cytotoxins / Q000378:metabolism; D018922:HL-60 Cells; D016480:Helicobacter pylori / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014617:Vacuoles / Q000378:metabolism
D001426:Bacterial Proteins; D003603:Cytotoxins; D009419:Nerve Tissue Proteins; C074689:VacA protein, Helicobacter pylori; C516895:PTPRZ1 protein, human; D017027:Protein Tyrosine Phosphatases; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5