title: YopH of Yersinia pseudotuberculosis interrupts early phosphotyrosine signalling associated with phagocytosis.
abstract: The PTPase YopH of Yersinia is essential to the ability of these bacteria to block phagocytosis. Wild-type Yersinia pseudotuberculosis, but not the yopH mutant strain, resisted phagocytosis by J774 cells. Ingestion of a yopH mutant was dependent on tyrosine kinase activity. Transcomplementation with wild-type yopH restored the anti-phagocytic effect, whereas introduction of the gene encoding the catalytically inactive yopHC403A was without effect. The PTPase inhibitor orthovanadate impaired the anti-phagocytic effect of the wild-type strain, further demonstrating the importance of bacteria-derived PTPase activity for this event. The ability to resist phagocytosis indicates that the effect of the bacterium is immediately exerted when it becomes associated with the phagocyte. Within 30 s after the onset of infection, wild-type Y. pseudotuberculosis caused a YopH-dependent dephosphorylation of phosphotyrosine proteins in J774 cells. Furthermore, interaction of the cells with phagocytosable strains led to a rapid and transient increase in tyrosine phosphorylation of paxillin and some other proteins, an event dependent on the presence of the bacterial surface-located protein invasin. Co-infection with the phagocytosable strain and the wild-type strain abolished the induction of tyrosine phosphorylation. Taken together, the present findings demonstrate an immediate YopH-mediated dephosphorylation of macrophage phosphotyrosine proteins, suggesting that this PTPase acts by preventing early phagocytosis-linked signalling in the phagocyte.
authors.affiliation: Department of Medical Microbiology, Linköping University, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Andersson
authors.forename: N
authors.initials: N
authors.lastname: Carballeira
authors.forename: K E
authors.initials: KE
authors.lastname: Magnusson
authors.forename: C
authors.initials: C
authors.lastname: Persson
authors.forename: O
authors.initials: O
authors.lastname: Stendahl
authors.forename: H
authors.initials: H
authors.lastname: Wolf-Watz
authors.forename: M
authors.initials: M
authors.lastname: Fällman
mesh_terms: D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D051379:Mice; D010587:Phagocytosis / Q000502:physiology; D019000:Phosphotyrosine / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000502:physiology*; D015011:Yersinia pseudotuberculosis / Q000235:genetics / Q000378:metabolism*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases; C067571:yopH protein, Yersinia