Bruton's tyrosine kinase-mediated interleukin-2 gene activation in mast cells. Dependence on the c-Jun N-terminal kinase activation pathway.

The Journal of Biological Chemistry
D HataT Kawakami

Abstract

Cross-linking of the high affinity IgE receptor (FcepsilonRI) on mast cells induces secretion of cytokines, including interleukin (IL)-2, through transcriptional activation of cytokine genes. Previously, defects in the gene coding for Bruton's tyrosine kinase (Btk) were shown to result in defective cytokine production in mast cells, and thereby mice carrying btk mutations exhibited diminished anaphylactic reactions in response to IgE and antigen. In this study, we provide evidence that the transcription factors involved in the IL-2 gene expression in T cells are also required for maximal activation of the IL-2 gene in FcepsilonRI-stimulated mast cells. Among them, AP-1 (Jun/Fos) and NF-AT were identified as candidate transcription factors that are regulated by Btk. Consistent with our previous data indicating that Btk regulates stress-activated protein kinases, c-Jun N-terminal kinase (JNK), c-Jun and other JNK-regulatable transcription factors are activated by FcepsilonRI cross-linking in a Btk-dependent manner. Further, FcepsilonRI-induced IL-2 gene activation is dependent on c-Jun and a component, SEK1, of its upstream activation pathway. Collectively, these data demonstrate that Btk regulates the transcription of the IL-2 g...Continue Reading

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Citations

Jun 23, 2001·Immunity·K AsaiT Kawakami
Feb 14, 2006·Nature Reviews. Immunology·Alasdair M Gilfillan, Christine Tkaczyk
Sep 7, 2000·The Journal of Experimental Medicine·J KitauraT Kawakami
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Feb 11, 2012·Critical Reviews in Immunology·Alasdair M Gilfillan, Michael A Beaven
Oct 22, 2003·Proceedings of the National Academy of Sciences of the United States of America·Jiro KitauraToshiaki Kawakami
Jun 15, 2000·Proceedings of the National Academy of Sciences of the United States of America·Y KawakamiT Kawakami
Mar 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·Y KawakamiT Kawakami
Sep 5, 2015·Pflügers Archiv : European journal of physiology·Math P CuajungcoJessica A Valadez
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Mar 28, 2007·International Immunopharmacology·Runa SurRavi Malaviya
Nov 3, 2006·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Hyo-Hyun ParkSang-Hyun Kim
Apr 25, 2018·International Journal of Molecular Sciences·Anna Tankiewicz-KwedloDariusz Pawlak
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Jul 21, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·Y KawakamiT Kawakami
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Mar 23, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mari Maeda-YamamotoToshiaki Kawakami
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Mar 6, 2007·The Journal of Allergy and Clinical Immunology·Taku Kambayashi, Gary A Koretzky

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