TPL2-mediated activation of ERK1 and ERK2 regulates the processing of pre-TNF alpha in LPS-stimulated macrophages

Journal of Cell Science
Simon RousseauPhilip Cohen

Abstract

Activation of the TPL2-MKK1/2-ERK1/2 signalling pathway is essential for lipopolysaccharide (LPS)-stimulated production of TNF alpha in macrophages. Here, we demonstrate that, unexpectedly, TPL2-deficient or MKK1-inhibited macrophages produce near normal levels of pre-TNF alpha when TLR2, TLR4 and TLR6 are activated by their respective agonists, but fail to secrete TNFalpha. We show that LPS stimulates the appearance of pre-TNFalpha at the cell surface and that this is prevented by inhibition of MAPK kinases 1 and 2 (MKK1/2) or in TPL2-deficient macrophages. However, the transport of pre-TNF alpha from the Golgi to the plasma membrane is unaffected by inhibition of the TPL2-MKK1/2-ERK1/2 pathway. Finally, we show that TACE, the protease that cleaves pre-TNF alpha to secreted TNFalpha, is phosphorylated by ERK1 and ERK2 (ERK1/2) at Thr735 in LPS-stimulated macrophages. Therefore, although TACE activity per se is not required for the LPS-stimulated cell surface expression of pre-TNF alpha, the phosphorylation of this protease might contribute to, or be required for, the cell surface expression of the pre-TNF alpha-TACE complex.

References

Jul 11, 1998·The Journal of Biological Chemistry·M F FavataJ M Trzaskos
Jul 8, 1999·Nature Medicine·J S Sebolt-LeopoldA R Saltiel
Mar 22, 2001·The New England Journal of Medicine·E H Choy, G S Panayi
Jul 26, 2003·The EMBO Journal·Aristides G EliopoulosPhilip N Tsichlis
Oct 15, 2003·Clinical Microbiology Reviews·S Janssens, R Beyaert
Jul 20, 2004·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·John Milton LucocqGareth Griffiths
Nov 12, 2005·Science·Rachael Z MurrayJennifer L Stow
Apr 1, 2006·Cellular Signalling·Simon RousseauPhilip Cohen
Apr 25, 2006·Nature Immunology·Stamatia PapoutsopoulouSteven C Ley
Jul 20, 2006·The Biochemical Journal·Simon MortonSimon Rousseau
Sep 14, 2007·The Biochemical Journal·Jenny BainPhilip Cohen

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Citations

Aug 25, 2011·Medical Microbiology and Immunology·Anna RoseMargaret J Dallman
Aug 4, 2010·Journal of Molecular Neuroscience : MN·Astrid V FahlenkampCordian Beyer
Jun 2, 2009·Nature Reviews. Drug Discovery·Matthias GaestelMichael Kracht
Aug 31, 2013·Nature Reviews. Molecular Cell Biology·Kristopher ClarkPhilip Cohen
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Owen M SiggsBruce Beutler
Jun 27, 2012·Proceedings of the National Academy of Sciences of the United States of America·Ana RiscoAna Cuenda
Aug 26, 2010·The Journal of Biological Chemistry·Irene Soria-CastroSusana Alemany
Aug 12, 2009·The Journal of Experimental Medicine·Frank KaiserAnne O'Garra
Aug 10, 2011·The Journal of Experimental Medicine·Monica GumaMichael Karin
Jun 27, 2012·Molecular and Cellular Biology·Huei-Ting YangSteven C Ley
Aug 5, 2010·Journal of Cell Science·Huijie LiuYi-Ping Li
Dec 8, 2010·Critical Reviews in Eukaryotic Gene Expression·Narayanan Parameswaran, Sonika Patial
Mar 22, 2014·Seminars in Immunology·Guadalupe Sabio, Roger J Davis
Feb 26, 2013·Leukemia & Lymphoma·Fotis AsimakopoulosPeiman Hematti
Feb 28, 2015·International Journal of Molecular Sciences·Hye Won LeeDo-Hyun Nam
Sep 3, 2008·The Journal of Cell Biology·Michele A WestColin Watts
Mar 8, 2011·Cancer Letters·Maria VougioukalakiAristides G Eliopoulos
Mar 8, 2011·Journal of Hazardous Materials·Mohd Imran KhanIqbal Ahmad
Feb 17, 2009·Current Opinion in Cell Biology·Philip Cohen
Feb 26, 2009·Oral Microbiology and Immunology·N BostanciG N Belibasakis
Mar 23, 2012·Immunological Reviews·Thorsten GantkeSteven C Ley
Oct 20, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Maria J PerugorriaDerek A Mann
Aug 2, 2013·Journal of Cellular Biochemistry·Megan HullNarayanan Parameswaran
Nov 6, 2013·Journal of Neurochemistry·Joshua HirschhornNarayan R Bhat
Feb 27, 2010·European Journal of Immunology·Ivo BendixSonia Waiczies
Jan 24, 2014·Biochemical Society Transactions·Kristopher Clark
Dec 3, 2014·European Journal of Pharmacology·Francisco J CaballeroMarco A Calzado
Jul 8, 2014·Oncogene·D C KanellisA G Eliopoulos
Oct 19, 2013·Biochimica Et Biophysica Acta·Jeanette SchwarzAthena Chalaris
Jun 8, 2012·Molecular Biology of the Cell·Marta López-PelaézSusana Alemany

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