Toxoplasma Rhoptry Protein 16 (ROP16) subverts host function by direct tyrosine phosphorylation of STAT6

Yi Ching Ong, Michael L. Reese, John C. Boothroyd

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

The obligate intracellular parasite, Toxoplasma gondii, modulates host immunity in a variety of highly specific ways. Previous work revealed a polymorphic, injected parasite factor, ROP16, to be a key virulence determinant and regulator of host cell transcription. These properties were shown to be partially mediated by dysregulation of the host transcription factors STAT3 and STAT6, but the molecular mechanisms underlying this phenotype were unclear. Here, we use a Type I Toxoplasma strain deficient in ROP16 to show that ROP16 induces not only sustained activation but also an extremely rapid (within 1 min) initial activation of STAT6. Using recombinant wild-type and kinase-deficient ROP16, we demonstrate in vitro that ROP16 has intrinsic tyrosine kinase activity and is capable of directly phosphorylating the key tyrosine residue for STAT6 activation, Tyr641. Furthermore, ROP16 co-immunoprecipitates with STAT6 from infected cells. Taken together, these data strongly suggest that STAT6 is a direct substrate for ROP16 in vivo.

Original languageEnglish (US)
Pages (from-to)28731-28740
Number of pages10
JournalJournal of Biological Chemistry
Volume285
Issue number37
DOIs
StatePublished - Sep 10 2010

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Phosphorylation
Toxoplasma
Tyrosine
Proteins
Chemical activation
Parasites
STAT6 Transcription Factor
STAT3 Transcription Factor
Transcription
Protein-Tyrosine Kinases
Virulence
Immunity
Phosphotransferases
Phenotype
Substrates

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Toxoplasma Rhoptry Protein 16 (ROP16) subverts host function by direct tyrosine phosphorylation of STAT6. / Ong, Yi Ching; Reese, Michael L.; Boothroyd, John C.

In: Journal of Biological Chemistry, Vol. 285, No. 37, 10.09.2010, p. 28731-28740.

Research output: Contribution to journalArticle

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