title: Tyrosine phosphatase MptpA of Mycobacterium tuberculosis inhibits phagocytosis and increases actin polymerization in macrophages.
abstract: Protein tyrosine phosphatases from several microorganisms have been shown to play a role as virulence factors by modifying the phosphorylation/dephosphorylation equilibrium in cells of their host. Two tyrosine phosphatases, MptpA and MptpB, secreted by Mycobacterium tuberculosis, have been identified. Expression of MptpA is upregulated upon infection of monocytes, but its role in host cells has not been elucidated. A eukaryotic expression vector containing the mptpA cDNA has been transfected into macrophages. We report that MptpA reduced phagocytosis of mycobacteria, opsonized zymosan or zymosan, but had no effect on phagocytosis of IgG-coated particles. We also noted that the presence of F-actin at the surface of phagosomes containing opsonized zymosan was significantly increased in cells expressing MptpA. In the presence of recombinant MptpA, the process of actin polymerization at the surface of isolated phagosomes was increased; this was not the case in the presence of the phosphatase-dead mutant MptpA(C11S). MptpA had no effect when IgG-coated particles were present inside isolated phagosomes. These results indicate that, like other tyrosine phosphatases of pathogens, MptpA plays a role in phagocytosis and actin polymerization. However, MptpA had no effect on IgG particles, suggesting that its putative substrate(s) is not linked to the signaling pathways of Fcgamma receptors.
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale, UMR CNRS 5089, 205 Route de Narbonne, 31077 Toulouse Cedex, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Castandet
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Prost
authors.forename: Pascale
authors.initials: P
authors.lastname: Peyron
authors.forename: Catherine
authors.initials: C
authors.lastname: Astarie-Dequeker
authors.forename: Elsa
authors.initials: E
authors.lastname: Anes
authors.forename: Alain J
authors.initials: AJ
authors.lastname: Cozzone
authors.forename: Gareth
authors.initials: G
authors.lastname: Griffiths
authors.forename: Isabelle
authors.initials: I
authors.lastname: Maridonneau-Parini
mesh_terms: D000199:Actins / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000201:enzymology / Q000472:pathogenicity*; D041681:NIH 3T3 Cells; D010587:Phagocytosis / Q000187:drug effects*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D014162:Transfection
chemical_list: D000199:Actins; D001426:Bacterial Proteins; C414465:MptpA protein, Mycobacterium tuberculosis; D011993:Recombinant Fusion Proteins; D017027:Protein Tyrosine Phosphatases