B-Raf contributes to sustained extracellular signal-regulated kinase activation associated with interleukin-2 production stimulated through the T cell receptor.

The Journal of Biological Chemistry
Hirotake TsukamotoYasuharu Nishimura

Abstract

A T cell receptor (TCR) recognizes and responds to an antigenic peptide in the context of major histocompatibility complex-encoded molecules. This provokes T cells to produce interleukin-2 (IL-2) through extracellular signal-regulated kinase (ERK) activation. We investigated the roles of B-Raf in TCR-mediated IL-2 production coupled with ERK activation in the Jurkat human T cell line. We found that TCR cross-linking could induce up-regulation of both B-Raf and Raf-1 activities, but Raf-1 activity was decreased rapidly. On the other hand, TCR-stimulated kinase activity of B-Raf was sustained. Expression of a dominant-negative mutant of B-Raf abrogated sustained but not transient TCR-mediated MEK/ERK activation. The inhibition of sustained ERK activation by either expression of a dominant-negative B-Raf or treatment with a MEK inhibitor resulted in a decrease of the TCR-stimulated nuclear factor of activated T cells (NFAT) activity and IL-2 production. Collectively, our data provide the first direct evidence that B-Raf is a positive regulator of TCR-mediated sustained ERK activation, which is required for NFAT activation and the full production of IL-2.

References

Jun 11, 1992·Nucleic Acids Research·M J van den HoffW H Lamers
Oct 6, 1995·The Journal of Biological Chemistry·J V BarnierG Calothy
Mar 1, 1994·European Journal of Immunology·D D'AmbrosioR Testi
Dec 1, 1995·European Journal of Immunology·D A Taylor-Fishwick, J N Siegel
Jan 19, 1996·The Journal of Biological Chemistry·T OhtsukaY Takai
Nov 29, 1996·The Journal of Biological Chemistry·N I PathanM L Harrison
Feb 14, 1997·The Journal of Biological Chemistry·R MaraisC J Marshall
Jul 1, 1997·Nature Genetics·L WojnowskiA Zimmer
Oct 10, 1998·Mechanisms of Development·L WojnowskiA Zimmer
Apr 10, 1999·The Journal of Biological Chemistry·M R van den BrinkS J Burakoff
Dec 2, 1999·Experimental Cell Research·C Hagemann, U R Rapp
Feb 29, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·U BommhardtT Hünig
Apr 13, 2000·European Journal of Immunology·S MariathasanP S Ohashi
Apr 27, 2000·Current Opinion in Immunology·L P KaneA Weiss
Apr 27, 2000·Current Opinion in Immunology·E Genot, D A Cantrell
Jun 19, 2001·Current Opinion in Immunology·M Rincón
Oct 24, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·S MariathasanP S Ohashi
Apr 10, 2002·The Journal of Biological Chemistry·Zipora BorovskyJacob Rachmilewitz
Sep 24, 2002·The Journal of Biological Chemistry·Xiaoqin XiangZhijun Luo
Jan 9, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yasushi UemuraYasuharu Nishimura
Sep 17, 2003·Genes & Development·Patrick G HoganAnjana Rao
Feb 7, 2004·The Journal of Biological Chemistry·Lucinda F ReynoldsVictor L J Tybulewicz
May 15, 2004·Proceedings of the National Academy of Sciences of the United States of America·Makoto OhtsukaTakashi Saito

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Citations

Sep 19, 2009·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Matthew R SilverDivya Chaudhary
Aug 21, 2010·Immunologic Research·Robert L Furler, Christel H Uittenbogaart
Jul 27, 2007·Science's STKE : Signal Transduction Knowledge Environment·Qian Qi, Avery August
Sep 5, 2014·Journal of Cellular Physiology·Hyun-Jung ParkHyung-Ryong Kim
Mar 10, 2012·Current Opinion in Pharmacology·Derek S Johnson, Youhai H Chen
Apr 10, 2013·Biochemical and Biophysical Research Communications·Hajime YurugiHiroshi Nakada
Sep 3, 2009·British Journal of Cancer·R J FlockhartP E Lovat
Jun 9, 2006·European Journal of Immunology·Nathalie Auphan-AnezinAnne-Marie Schmitt-Verhulst
Jun 23, 2006·European Journal of Immunology·Hirotake TsukamotoYasuharu Nishimura
Jan 30, 2008·European Journal of Immunology·Hirotake TsukamotoYasuharu Nishimura
Jun 24, 2017·Immunity & Ageing : I & a·Ling HuangMichiel G H Betjes
Nov 5, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nelson K Y WongPauline Johnson
Jan 30, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sumit DeswalWolfgang W A Schamel
Oct 3, 2006·Cellular Signalling·Alison Hindley, Walter Kolch

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