M. tuberculosis PknG manipulates host autophagy flux to promote pathogen intracellular survival.

Autophagy
Pupu GeJing Wang

Abstract

The eukaryotic-type protein kinase G (PknG), one of the eleven eukaryotic type serine-threonine protein kinase (STPK) in Mycobacterium tuberculosis (Mtb), is involved in mycobacterial survival within macrophages, presumably by suppressing phagosome and autophagosome maturation, which makes PknG an attractive drug target. However, the exact mechanism by which PknG inhibits pathogen clearance during mycobacterial infection remains largely unknown. Here, we show that PknG promotes macroautophagy/autophagy induction but inhibits autophagosome maturation, causing an overall effect of blocked autophagy flux and enhanced pathogen intracellular survival. PknG prevents the activation of AKT (AKT serine/threonine kinase) via competitively binding to its pleckstrin homology (PH) domain, leading to autophagy induction. Remarkably, PknG could also inhibit autophagosome maturation to block autophagy flux via targeting host small GTPase RAB14. Specifically, PknG directly interacts with RAB14 to block RAB14-GTP hydrolysis. Furthermore, PknG phosphorylates TBC1D4/AS160 (TBC1 domain family member 4) to suppress its GTPase-activating protein (GAP) activity toward RAB14. In macrophages and in vivo, PknG promotes Mtb intracellular survival through ...Continue Reading

References

Jul 1, 1975·The British Journal of Dermatology·P D Mier, J J van den Hurk
Apr 29, 2000·Trends in Microbiology·Y Av-Gay, M Everett
May 1, 2004·The Journal of Experimental Medicine·Jonathan C KaganCraig R Roy
Feb 19, 2005·Science·D D SarbassovDavid M Sabatini
Mar 9, 2005·Proceedings of the National Academy of Sciences of the United States of America·Isabelle VergneVojo Deretic
Jun 24, 2005·The Biochemical Journal·Cristinel P MîineaGustav E Lienhard
Aug 31, 2006·Cellular Microbiology·Hubert Hilbi
Oct 13, 2006·Nature·Gilbert Di Paolo, Pietro De Camilli
Jul 10, 2007·Proceedings of the National Academy of Sciences of the United States of America·Nicole ScherrMichel O Steinmetz
Sep 18, 2007·Biochimica Et Biophysica Acta·Annemarie WehenkelPedro M Alzari
Sep 12, 2008·Cellular Microbiology·Jennifer A Philips
Jun 17, 2009·Cell Host & Microbe·Yadunanda Kumar, Raphael H Valdivia
Jul 16, 2009·Nature Reviews. Molecular Cell Biology·Harald Stenmark
Aug 6, 2009·Annual Review of Genetics·Congcong He, Daniel J Klionsky
Sep 11, 2009·The Journal of Biological Chemistry·Grantley R PeckGustav E Lienhard
Oct 30, 2010·Journal of Cellular and Molecular Medicine·Uxía Gurriarán-RodríguezJesús P Camiña
Nov 17, 2011·Proceedings of the National Academy of Sciences of the United States of America·Dennis WongYossef Av-Gay
May 9, 2012·Trends in Immunology·Gregory D Fairn, Sergio Grinstein
Sep 6, 2013·Nature·Paolo S ManzanilloJeffery S Cox
Aug 28, 2014·American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions·Hong YaoXiuzhen Han
Oct 10, 2014·Cell Host & Microbe·Nora MelloukJost Enninga
Nov 28, 2014·Microbiology Spectrum·Sladjana Prisic, Robert N Husson
Feb 6, 2015·The Journal of Clinical Investigation·Vojo DereticMichael Mandell
Jun 18, 2015·Frontiers in Cellular and Infection Microbiology·Lucile EspertIsabelle Vergne
Sep 19, 2015·Nature Immunology·Shusaku T ShibutaniTamotsu Yoshimori
Jan 15, 2016·Journal of Cell Science·Caroline MauvezinThomas P Neufeld
Feb 24, 2016·The Journal of Clinical Investigation·Thomas R LernerMaximiliano G Gutierrez
Nov 21, 2016·Cellular and Molecular Life Sciences : CMLS·Jane Atesoh Awuh, Trude Helen Flo

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