title: Morphologic differentiation of HL-60 cells is associated with appearance of RPTPbeta and induction of Helicobacter pylori VacA sensitivity.
abstract: Phorbol 12-myristate 13-acetate (PMA) induces differentiation of human leukemic HL-60 cells into cells with macrophage-like characteristics and enhances the susceptibility of HL-60 cells to the Helicobacter pylori VacA toxin (de Bernard, M., Moschioni., M., Papini, E., Telford, J. L., Rappuoli, R., and Montecucco, C. (1998) FEBS Lett. 436, 218-222). We examined the mechanism by which HL-60 cells acquire sensitivity to VacA, in particular, looking for expression of RPTPbeta, a VacA-binding protein postulated to be the VacA receptor (Yahiro, K., Niidome, T., Kimura, M., Hatakeyama, T., Aoyagi, H., Kurazono, H., Imagawa, K., Wada, A., Moss, J., and Hirayama, T. (1999) J. Biol. Chem. 274, 36693-36699). PMA induced expression of RPTPbeta mRNA and protein as determined by RNase protection assay and indirect immunofluorescence studies, respectively. Vitamin D(3) and interferon-gamma, which stimulate differentiation of HL-60 cells into monocyte-like cells, also induced VacA sensitivity and expression of RPTPbeta mRNA, whereas 1. 2% Me(2)SO and retinoic acid, which stimulated the maturation of HL-60 into granulocyte-like cells, did not. RPTPbeta antisense oligonucleotide inhibited induction of VacA sensitivity and expression of RPTPbeta. Double immunostaining studies also indicated that newly expressed RPTPbeta colocalized with VacA in PMA-treated HL-60 cells. In agreement with these data, BHK-21 cells, which are insensitive to VacA, when transfected with the RPTPbeta cDNA, acquired VacA sensitivity. All data are consistent with the conclusion that acquisition of VacA sensitivity by PMA-treated HL-60 cells results from induction of RPTPbeta, a protein that functions as the VacA receptor.
authors.affiliation: Department of Bacteriology, Institute of Tropical Medicine, Nagasaki University, Japan.
authors.forename: P I
authors.initials: PI
authors.lastname: Padilla
authors.forename: A
authors.initials: A
authors.lastname: Wada
authors.forename: K
authors.initials: K
authors.lastname: Yahiro
authors.forename: M
authors.initials: M
authors.lastname: Kimura
authors.forename: T
authors.initials: T
authors.lastname: Niidome
authors.forename: H
authors.initials: H
authors.lastname: Aoyagi
authors.forename: A
authors.initials: A
authors.lastname: Kumatori
authors.forename: M
authors.initials: M
authors.lastname: Anami
authors.forename: T
authors.initials: T
authors.lastname: Hayashi
authors.forename: J
authors.initials: J
authors.lastname: Fujisawa
authors.forename: H
authors.initials: H
authors.lastname: Saito
authors.forename: J
authors.initials: J
authors.lastname: Moss
authors.forename: T
authors.initials: T
authors.lastname: Hirayama
mesh_terms: D001426:Bacterial Proteins / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D002762:Cholecalciferol / Q000494:pharmacology; D005786:Gene Expression Regulation; D018922:HL-60 Cells; D016480:Helicobacter pylori; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007700:Kinetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D011956:Receptors, Cell Surface / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014158:Transcription, Genetic; D014212:Tretinoin / Q000494:pharmacology; D014617:Vacuoles / Q000187:drug effects*
chemical_list: D001426:Bacterial Proteins; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; D011956:Receptors, Cell Surface; D013873:Thionucleotides; C074689:VacA protein, Helicobacter pylori; D002762:Cholecalciferol; D014212:Tretinoin; D007371:Interferon-gamma; C516895:PTPRZ1 protein, human; D017027:Protein Tyrosine Phosphatases; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D013755:Tetradecanoylphorbol Acetate