Inhibition of Akt/GSK3beta signalling pathway by Legionella pneumophila is involved in induction of T-cell apoptosis

The Biochemical Journal
Reika TakamatsuNaoki Mori

Abstract

Legionella pneumophila is the causative agent of human Legionnaires' disease. L. pneumophila has been shown to induce apoptosis of T-cells and this may be important pathologically and clinically. The present study has determined the molecular mechanisms underlying L. pneumophila-induced apoptosis, which were unclear. Wild-type L. pneumophila and flagellin-deficient Legionella, but not L. pneumophila lacking a functional type IV secretion system Dot/Icm, replicated in T-cells. However, apoptosis was efficiently induced in T-cells only by wild-type L. pneumophila, and not flagellin-deficient or Dot/Icm-deficient Legionella. Induction of apoptosis involved activation of the initiator caspase 9 and effector caspase 3. Infection with L. pneumophila inhibited phosphorylation of Akt (also known as protein kinase B) and the Akt substrate GSK3beta (glycogen synthase kinase 3beta), and reduced the levels of beta-catenin, a transcriptional activator regulated by GSK3beta. It also caused the activation of the pro-apoptotic protein Bax and inhibited the expression of the anti-apoptotic protein XIAP (X-linked inhibitor of apoptosis) via inhibition of the Akt pathway. In conclusion, L. pneumophila induces mitochondria-mediated T-cell apoptosi...Continue Reading

References

Jan 7, 1998·The Journal of Cell Biology·K G WolterR J Youle
Jul 8, 1999·Proceedings of the National Academy of Sciences of the United States of America·P H EdelsteinS Falkow
Sep 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·G S Salvesen, V M Dixit
Nov 5, 1999·Annual Review of Microbiology·Y Weinrauch, A Zychlinsky
Oct 12, 2000·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·J M WalzB Neumeister
Feb 14, 2002·The Journal of Biological Chemistry·Fuminori TsurutaYukiko Gotoh
Sep 10, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lauren S Collier-HyamsAndrew S Neish
Nov 13, 2002·Microbiology·Birgid NeumeisterSebastian Wesselborg
Nov 26, 2002·Nature Cell Biology·Jonathan C Kagan, Craig R Roy
Mar 7, 2003·FEMS Microbiology Letters·Patrick WeissgerberBirgid Neumeister
Dec 3, 2003·The Journal of Biological Chemistry·Han C DanJin Q Cheng
Aug 20, 2004·Journal of Medicinal Chemistry·Thorsten K OostStephen W Fesik
Oct 8, 2004·Cellular Microbiology·Annie L Neild, Craig R Roy
Dec 3, 2005·Cell Death and Differentiation·A D SchimmerS J Riedl
Apr 12, 2006·The Journal of Experimental Medicine·Ari B MolofskyMichele S Swanson
Sep 21, 2006·The Journal of Biological Chemistry·Amal AmerGabriel Núñez
May 12, 2007·Journal of Virology·Arnaud AutretBruno Blondel
Jul 3, 2007·Cell·Brendan D Manning, Lewis C Cantley
Oct 13, 2007·Journal of Molecular and Cellular Cardiology·Masahiro NishiharaKazuaki Shimamoto
Jun 21, 2008·Cell Death and Differentiation·K Labbé, M Saleh
Aug 22, 2009·Journal of the American Society of Nephrology : JASN·Zhiyong WangSteven C Borkan

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Citations

Jul 25, 2013·The International Journal of Biochemistry & Cell Biology·Wei LiuHuijun Duan
Nov 22, 2011·PLoS Pathogens·Catherine M MillerNicholas C Smith

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