Morphologic differentiation of HL-60 cells is associated with appearance of RPTPβ and induction of Helicobacter pylori VacA sensitivity

Philip Ian Padilla, Akihiro Wada, Kinnosuke Yahiro, Miyuki Kimura, Takuro Niidome, Haruhiko Aoyagi, Atsushi Kumatori, Masanobu Anami, Tomoyoshi Hayashi, Jun Ichi Fujisawa, Haruo Saito, Joel Moss, Toshiya Hirayama

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68 Citations (Scopus)


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 RPTPβ, 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 RPTPβ mRNA and protein as determined by RNase protection assay and indirect immunofluorescence studies, respectively. Vitamin D3 and interferon-γ, which stimulate differentiation of HL-60 cells into monocyte-like cells, also induCed VacA sensitivity and expression of RPTPβ mRNA, whereas 1.2% Me2SO and retinoic acid, which stimulated the maturation of HL-60 into granulocyte- like cells, did not. RPTPβ antisense oligonucleotide inhibited induction of VacA sensitivity and expression of RPTPβ. Double immunostaining studies also indicated that newly expressed RPTPβ 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 RPTPβ 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 RPTPβ, a protein that functions as the VacA receptor.

Original languageEnglish
Pages (from-to)15200-15206
Number of pages7
JournalJournal of Biological Chemistry
Issue number20
Publication statusPublished - May 19 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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