Yersinia phosphatase induces mitochondrially dependent apoptosis of T cells

J Biol Chem. 2005 Mar 18;280(11):10388-94. doi: 10.1074/jbc.M408829200. Epub 2005 Jan 4.


To evade the immune system, the etiologic agent of plague, Yersinia pestis, injects an exceptionally active tyrosine phosphatase called YopH into host cells using a type III secretion system. We recently reported that YopH acutely inhibits T cell antigen receptor signaling by dephosphorylating the Lck tyrosine kinase. Here, we show that prolonged presence of YopH in primary T cells or Jurkat T leukemia cells causes apoptosis, detected by annexin V binding, mitochondrial breakdown, caspase activation, and internucleosomal fragmentation. YopH also causes cell death when expressed in HeLa cells, and this cell death was inhibited by YopH-specific small molecule inhibitors. Cell death induced by YopH was also prevented by caspase inhibition or co-expression of Bcl-xL. We conclude that YopH not only paralyzes T cells acutely, but also ensures that the cells will not recover to induce a protective immune response but instead undergo mitochondrially regulated programmed cell death.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Annexin A5 / chemistry
  • Annexin A5 / pharmacology
  • Apoptosis*
  • Bacterial Outer Membrane Proteins / metabolism
  • Bacterial Outer Membrane Proteins / physiology*
  • Caspases / metabolism
  • Cell Death
  • Cell Separation
  • DNA Fragmentation
  • Enzyme Activation
  • Flow Cytometry
  • HeLa Cells
  • Humans
  • Jurkat Cells
  • Mitochondria / metabolism
  • Mitochondria / pathology*
  • Mutagenesis, Site-Directed
  • Nucleosomes / metabolism
  • Phosphorylation
  • Protein Tyrosine Phosphatases / metabolism
  • Protein Tyrosine Phosphatases / physiology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction
  • T-Lymphocytes / cytology
  • T-Lymphocytes / pathology*
  • Transfection
  • Yersinia pestis / enzymology*
  • bcl-X Protein


  • Annexin A5
  • BCL2L1 protein, human
  • Bacterial Outer Membrane Proteins
  • Nucleosomes
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-X Protein
  • Protein Tyrosine Phosphatases
  • yopH protein, Yersinia
  • Caspases