Document Detail


The cell-specific phenotype of the polymorphic vacA midregion is independent of the appearance of the cell surface receptor protein tyrosine phosphatase beta.
MedLine Citation:
PMID:  16368956     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
There are two alleles, m1 and m2, of the midregion of the vacuolating cytotoxin gene (vacA) of Helicobacter pylori which code for toxins with different cell specificities. Here we describe the construction of five chimeric strains in which regions of vacA were exchanged between the two genotypes. By analyzing the toxicity of these strains for HeLa and RK13 cells we have confirmed that a 148-amino-acid region determines the phenotypic differences between the two forms of the protein and that this entire region is important for cytotoxicity. Furthermore, we have used our chimeric strains to investigate whether variations in the midregion of VacA have an effect on phorbol 12-myristate 13-acetate (PMA)-induced VacA sensitivity in HL-60 cells. The PMA-induced VacA sensitivity of HL-60 cells has been previously associated with the appearance of the cell surface receptor protein tyrosine phosphatase beta (RPTPbeta). Our data indicate that both the m1 and m2 forms of VacA are able to utilize RPTPbeta, and the cell-specific phenotype of the midregion is independent of the presence of RPTPbeta. It appears that another as-yet-unidentified receptor exists in HL-60 cells that accounts for the m2 phenotype in this cell line. Also, by studying the effect of PMA on levels of RPTPbeta in other cell lines and toxicity of VacA in these cell lines we have shown that RPTPbeta does not play a major role in the vacuolation of HeLa cells.
Authors:
David A G Skibinski; Christophe Genisset; Silvia Barone; John L Telford
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Infection and immunity     Volume:  74     ISSN:  0019-9567     ISO Abbreviation:  Infect. Immun.     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2005-12-21     Completed Date:  2006-02-07     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  0246127     Medline TA:  Infect Immun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  49-55     Citation Subset:  IM    
Affiliation:
IRIS, Chiron Srl, Via Fiorentina 1, 53100 Siena, Italy.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Bacterial Proteins / genetics*,  metabolism
HeLa Cells
Helicobacter pylori / drug effects,  enzymology*,  genetics*,  pathogenicity
Humans
Molecular Sequence Data
Nerve Tissue Proteins / physiology*
Phenotype
Polymorphism, Genetic
Protein Tyrosine Phosphatases / physiology*
Receptor-Like Protein Tyrosine Phosphatases, Class 5
Tetradecanoylphorbol Acetate / pharmacology
Chemical
Reg. No./Substance:
0/Bacterial Proteins; 0/Nerve Tissue Proteins; 0/VacA protein, Helicobacter pylori; 16561-29-8/Tetradecanoylphorbol Acetate; EC 3.1.3.48/PTPRZ1 protein, human; EC 3.1.3.48/Protein Tyrosine Phosphatases; EC 3.1.3.48/Receptor-Like Protein Tyrosine Phosphatases, Class 5
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