In this section
@article{Breyer:2021:10.15252/embj.2020106188,
author = {Breyer, F and Hartlova, A and Thurston, T and Flynn, HR and Chakravarty, P and Janzen, J and Peltier, J and Heunis, T and Snijders, AP and Trost, M and Ley, SC},
doi = {10.15252/embj.2020106188},
journal = {The EMBO Journal},
pages = {1--19},
title = {TPL-2 kinase induces phagosome acidification to promote macrophage killing of bacteria},
url = {http://dx.doi.org/10.15252/embj.2020106188},
volume = {40},
year = {2021}
}
TY - JOUR
AB - Tumour progression locus 2 (TPL-2) kinase mediates Toll-like receptor (TLR) activation of ERK1/2 and p38α MAP kinases in myeloid cells to modulate expression of key cytokines in innate immunity. This study identified a novel MAP kinase-independent regulatory function for TPL-2 in phagosome maturation, an essential process for killing of phagocytosed microbes. TPL-2 catalytic activity was demonstrated to induce phagosome acidification and proteolysis in primary mouse and human macrophages following uptake of latex beads. Quantitative proteomics revealed that blocking TPL-2 catalytic activity significantly altered the protein composition of phagosomes, particularly reducing the abundance of V-ATPase proton pump subunits. Furthermore, TPL-2 stimulated the phosphorylation of DMXL1, a regulator of V-ATPases, to induce V-ATPase assembly and phagosome acidification. Consistent with these results, TPL-2 catalytic activity was required for phagosome acidification and the efficient killing of Staphylococcus aureus and Citrobacter rodentium following phagocytic uptake by macrophages. TPL-2 therefore controls innate immune responses of macrophages to bacteria via V-ATPase induction of phagosome maturation.
AU - Breyer,F
AU - Hartlova,A
AU - Thurston,T
AU - Flynn,HR
AU - Chakravarty,P
AU - Janzen,J
AU - Peltier,J
AU - Heunis,T
AU - Snijders,AP
AU - Trost,M
AU - Ley,SC
DO - 10.15252/embj.2020106188
EP - 19
PY - 2021///
SN - 0261-4189
SP - 1
TI - TPL-2 kinase induces phagosome acidification to promote macrophage killing of bacteria
T2 - The EMBO Journal
UR - http://dx.doi.org/10.15252/embj.2020106188
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000641845500001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR - https://www.embopress.org/doi/full/10.15252/embj.2020106188
UR - http://hdl.handle.net/10044/1/89134
VL - 40
ER -
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