Multiple ITAM-coupled NK-cell receptors engage the Bcl10/Malt1 complex via Carma1 for NF-kappaB and MAPK activation to selectively control cytokine production

Blood
Olaf GrossJ Ruland

Abstract

Natural killer (NK) cells are innate immune cells that mediate resistance against viruses and tumors. They express multiple activating receptors that couple to immunoreceptor tyrosine-based activation motif (ITAM)-containing signaling chains for downstream cell activation. Ligation of activating NK-cell receptors induces NK-cell cytotoxicity and cytokine release. How these distinct events are selectively controlled is not well defined. Here we report the identification of a specific signaling pathway that operates downstream of the ITAM-coupled NK-cell receptors NK1.1, Ly49D, Ly49H, and NKG2D. Using primary NK cells from Bcl10(-/-), Malt1(-/-), Carma1(-/-), and Card9(-/-) mice, we demonstrate a key role for Bcl10 signalosomes in the activation of canonical NF-kappaB signaling as well as JNK and p38 MAPK upon NK-cell triggering. Bcl10 directly cooperates with Malt1 and depends on Carma1 (Card11) but not on Card9 for NK-cell activation. These Bcl10-dependent cascades selectively control cytokine and chemokine production but do not affect NK-cell differentiation or killing. Thus, we identify a molecular basis for the segregation of NK-cell receptor-induced signals for cytokine release and target cell killing and extend the previou...Continue Reading

References

Jun 10, 1997·Proceedings of the National Academy of Sciences of the United States of America·T IshizukaE W Gelfand
Sep 11, 2001·Nature Immunology·A O DokunW M Yokoyama
Mar 22, 2002·Nature Reviews. Immunology·A Cerwenka, L L Lanier
Apr 2, 2003·Nature Reviews. Immunology·Wayne M Yokoyama, Beatrice F M Plougastel
Jun 6, 2003·Current Opinion in Immunology·Lewis L Lanier
Jun 24, 2003·Immunity·Hiromitsu HaraJosef M Penninger
Oct 25, 2003·Science·Astrid A Ruefli-BrasseVishva M Dixit
May 4, 2004·Nature Reviews. Immunology·Margot Thome
Sep 15, 2004·The Journal of Experimental Medicine·Marina CellaWojciech Swat
Sep 17, 2004·Genes & Development·Matthew S Hayden, Sankar Ghosh
Sep 28, 2005·Nature Immunology·Shintaro SatoShizuo Akira
Oct 27, 2005·Blood·John R OrtaldoHoward A Young
Dec 17, 2005·Immunity·Karen SommerDavid J Rawlings
Jul 22, 2006·Proceedings of the National Academy of Sciences of the United States of America·Hong-Hsing LiuZhijian J Chen
Oct 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anthony R FrenchWayne M Yokoyama
Oct 26, 2006·Nature Reviews. Immunology·David J RawlingsMiguel E Moreno-García
Nov 15, 2006·Proceedings of the National Academy of Sciences of the United States of America·Linda M McAllister-LucasPeter C Lucas
Dec 5, 2006·Current Opinion in Immunology·Sheryl E Kirwan, Deborah N Burshtyn
Dec 22, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yuhong ChenDemin Wang
Apr 24, 2007·Nature Immunology·Salomé LeibundGut-LandmannCaetano Reis e Sousa
May 3, 2007·Science's STKE : Signal Transduction Knowledge Environment·Elmar Wegener, Daniel Krappmann
Sep 6, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Subramaniam MalarkannanDemin Wang

❮ Previous
Next ❯

Citations

Dec 2, 2010·Cell Research·Jens StaalRudi Beyaert
Dec 29, 2010·Cell Research·Marzenna Blonska, Xin Lin
Nov 26, 2009·Immunology and Cell Biology·Victoria G EmpsonNicola Dalbeth
Mar 20, 2009·Nature Immunology·Lionel B Ivashkiv
Oct 23, 2013·Nature Immunology·Eric VivierJacques A Nunès
May 15, 2010·Nature Reviews. Immunology·Attila MócsaiVictor L J Tybulewicz
Sep 8, 2010·Nature Reviews. Immunology·Petter Höglund, Petter Brodin
Nov 10, 2009·Proceedings of the National Academy of Sciences of the United States of America·Stephan HailfingerMargot Thome
Jul 21, 2011·The Journal of Biological Chemistry·Kamalakannan RajasekaranSubramaniam Malarkannan
Sep 8, 2011·The Journal of Biological Chemistry·Cinthia C StempinVanessa Redecke
Sep 23, 2008·The Journal of Biological Chemistry·Felicia D LangelBrian C Schaefer
Sep 24, 2008·The Journal of Experimental Medicine·Hailong GuoSubramaniam Malarkannan
Aug 26, 2009·The Journal of Experimental Medicine·Matthew J RobinsonCaetano Reis e Sousa
Aug 27, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Linda M McAllister-LucasPeter C Lucas
Dec 18, 2013·Immunology and Cell Biology·Lucas Ferrari de AndradeLudovic Martinet
Feb 12, 2013·Chemical Society Reviews·Dziyana KraskouskayaPatrick T Gunning
Sep 20, 2015·Biochimie·Janna Hachmann, Guy S Salvesen
Jan 21, 2016·Trends in Molecular Medicine·Annelies DemeyerRudi Beyaert
Feb 5, 2013·The Journal of Allergy and Clinical Immunology·Polina StepenskyKlaus Warnatz
Oct 29, 2015·Cellular and Molecular Life Sciences : CMLS·Maike Jaworski, Margot Thome
Apr 11, 2009·Trends in Immunology·Hiromitsu Hara, Takashi Saito
Mar 21, 2009·Seminars in Immunology·Donna L Farber
Jul 15, 2009·Immunological Reviews·Helen S GoodridgeDavid M Underhill
Dec 17, 2008·Annals of the New York Academy of Sciences·Jürgen Ruland
Sep 21, 2010·International Journal of Cancer. Journal International Du Cancer·Alessandro PoggiMaria Raffaella Zocchi
Jul 14, 2011·Cell Cycle·Shaun RosebeckLinda M McAllister-Lucas
Jun 1, 2016·Frontiers in Immunology·Kamalakannan RajasekaranSubramaniam Malarkannan
Jun 16, 2016·Proceedings of the National Academy of Sciences of the United States of America·Burak DuraJoel Voldman
Apr 1, 2017·Experimental & Molecular Medicine·Hyung-Joon KwonHun Sik Kim
Jan 9, 2009·European Journal of Immunology·Benjamin D MedoffRamnik J Xavier
Dec 6, 2018·Journal of Leukocyte Biology·Jeffrey D NansonThomas Ve
Nov 24, 2018·Nature Reviews. Immunology·Jürgen Ruland, Lara Hartjes
Jun 26, 2008·Nature Reviews. Immunology·Margot Thome
Jun 4, 2015·Molecular Systems Biology·Shankha SatpathyChunaram Choudhary
Nov 20, 2019·EMBO Reports·Ludmila Cardoso AlvesPhilippe Krebs
Dec 18, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Benjamin Joachim SchmiedelHelmut Rainer Salih
Dec 31, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jun ChenZusen Fan
Aug 25, 2011·Cellular and Molecular Life Sciences : CMLS·Alfonso Martín-FontechaHugh J M Brady

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