YopH of Yersinia pseudotuberculosis interrupts early phosphotyrosine signalling associated with phagocytosis

Mol Microbiol. 1996 Jun;20(5):1057-69. doi: 10.1111/j.1365-2958.1996.tb02546.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / metabolism*
  • Cell Line
  • Mice
  • Phagocytosis / physiology
  • Phosphotyrosine / metabolism*
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / metabolism*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Signal Transduction / physiology*
  • Yersinia pseudotuberculosis / genetics
  • Yersinia pseudotuberculosis / metabolism*

Substances

  • Bacterial Outer Membrane Proteins
  • Phosphotyrosine
  • Protein-Tyrosine Kinases
  • Protein Tyrosine Phosphatases
  • yopH protein, Yersinia