Toxoplasma rhoptry protein 16 (ROP16) subverts host function by direct tyrosine phosphorylation of STAT6.

The Journal of Biological Chemistry
Yi-Ching OngJohn C Boothroyd

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, Tyr(641). 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.

References

Jan 1, 1992·Molecular and Biochemical Parasitology·P N OssorioJ C Boothroyd
Dec 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·R McKendryG R Stark
Mar 1, 1990·The Journal of protozoology·T Endo, K Yagita
Oct 1, 1995·Molecular and Biochemical Parasitology·D SoldatiJ C Boothroyd
Feb 1, 1997·Molecular and Cellular Biology·F KohlhuberI M Kerr
Oct 6, 1999·American Journal of Respiratory and Critical Care Medicine·A TomkinsonE W Gelfand
Sep 13, 2000·The Journal of Biological Chemistry·Y Ohmori, T A Hamilton
Mar 17, 2001·The EMBO Journal·K Ribbeck, D Görlich
Apr 20, 2001·Proceedings of the National Academy of Sciences of the United States of America·V G TusherG Chu
Jul 28, 2001·The Journal of Infectious Diseases·M E GriggT P Margolis
Sep 7, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·J Hoeck, M Woisetschläger
Apr 12, 2002·Biochemical and Biophysical Research Communications·Bruno SchnyderRené Moser
Dec 7, 2002·Molecular and Biochemical Parasitology·Peter J BradleyJohn C Boothroyd
Feb 13, 2003·Nucleic Acids Research·Rafael A IrizarryTerence P Speed
Jun 5, 2003·The Journal of Biological Chemistry·Michael O DainesGurjit K Khurana Hershey
Sep 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zhi ChenRiitta Lahesmaa
Jan 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nives ZimmermannMarc E Rothenberg
Feb 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sharon H JacksonCharles E Egwuagu
Aug 6, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Amy S McKeeEdward J Pearce
Oct 14, 2004·Molecular and Biochemical Parasitology·B F C KafsackV B Carruthers
Dec 21, 2004·European Journal of Biochemistry·Thomas Meyer, Uwe Vinkemeier
May 17, 2005·Nature Immunology·Jessica A HamermanLewis L Lanier
Mar 17, 2006·Cytokine & Growth Factor Reviews·Daniel HebenstreitAlbert Duschl
Sep 9, 2006·Clinical Immunology : the Official Journal of the Clinical Immunology Society·David T Montag, Michael T Lotze
Dec 23, 2006·Annals of the New York Academy of Sciences·Fumihiko Hayakawa, Tomoki Naoe
Jan 18, 2007·Immunology and Cell Biology·Pamela J Gaddi, George S Yap
Apr 4, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Seon-Kyeong KimJohn C Boothroyd
May 16, 2007·Molecular Microbiology·John C Carmen, Anthony P Sinai
Dec 7, 2007·Nature Reviews. Microbiology·John C Boothroyd, Jean-Francois Dubremetz
Apr 11, 2008·Immunity·John J O'Shea, Peter J Murray
May 30, 2008·Frontiers in Bioscience : a Journal and Virtual Library·Dan Xu, Cheng-Kui Qu
Aug 19, 2008·Seminars in Cell & Developmental Biology·Ben A CrokerSandra E Nicholson
Apr 1, 2009·Emerging Infectious Diseases·Bernard CarmeMarie Laure Dardé
Jun 3, 2009·The Korean Journal of Parasitology·Hye-Jin AhnHo-Woo Nam

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Citations

May 18, 2013·Parasitology Research·Feng WeiQuan Liu
Apr 11, 2013·Trends in Parasitology·Natalie A CounihanTania F de Koning-Ward
Oct 17, 2012·Nature Reviews. Microbiology·Christopher A Hunter, L David Sibley
May 19, 2011·Proceedings of the National Academy of Sciences of the United States of America·Michael S BehnkeL David Sibley
Mar 26, 2011·Proceedings of the National Academy of Sciences of the United States of America·Michael L ReeseJon P Boyle
Jun 15, 2011·The Journal of Experimental Medicine·Masahiro YamamotoKiyoshi Takeda
Sep 21, 2011·Briefings in Functional Genomics·Dina R Weilhammer, Amy Rasley
Sep 14, 2011·Infection and Immunity·Pedro MorgadoMelissa B Lodoen
Aug 23, 2012·PLoS Pathogens·Anita A KoshyJohn C Boothroyd
Sep 28, 2013·International Journal for Parasitology·Ana CamejoJeroen P J Saeij
Feb 15, 2011·Journal of Proteomics·V Marugán-HernándezL M Ortega-Mora
Nov 13, 2013·Infection and Immunity·Sarah E EwaldJohn C Boothroyd
Apr 4, 2012·Expert Opinion on Drug Discovery·Chunmei JinHyun Park
Dec 14, 2011·International Journal for Parasitology·Daniel C LimJeroen P J Saeij
Sep 7, 2011·Trends in Parasitology·Mariane B MeloJeroen P J Saeij
Jun 11, 2011·Trends in Parasitology·Jessica S TylerJohn C Boothroyd
Apr 29, 2015·Current Opinion in Microbiology·Mohamed-Ali Hakimi, Alexandre Bougdour
Feb 26, 2011·Immunological Reviews·L David Sibley
Jul 21, 2011·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Sarah J Fentress, L David Sibley
Feb 28, 2015·International Journal for Parasitology·Louis-Philippe LerouxFlorence S Dzierszinski
Jan 3, 2012·Parasitology International·Kentaro KatoTatsuya Iwanaga

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