PXD020401-1

PXD020401 is an original dataset announced via ProteomeXchange.

Title	TPL-2 kinase induces phagosome acidification to promote macrophage killing of Staphylococcus aureus
Description	Tumor Progression Locus 2 (TPL-2) kinase mediates Toll-like Receptor (TLR) activation of ERK1/2 and p38-alpha 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 bacteria. TPL-2 catalytic activity was demonstrated to induce phagosome acidification and proteolysis in primary mouse and human macrophages following uptake of latex beads. Mass spectrometry analysis 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 was shown to stimulate the phosphorylation of DMXL1, a critical regulator of V-ATPases, to induce phagosome acidification. Consistent with these results, TPL-2 catalytic activity was required for phagosome acidification, activation of phagosome acid-sensitive cathepsins and the efficient killing of Staphylococcus aureus following phagocytic uptake by macrophages. These results indicate that TPL-2 controls the innate immune response of macrophages to bacteria via MAP kinase regulation of gene expression and V-ATPase induction of phagosome maturation.
HostingRepository	PRIDE
AnnounceDate	2021-02-11
AnnouncementXML	Submission_2021-02-11_04:30:11.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Matthias Trost
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-16 06:53:24	ID requested
⏵ 1	2021-02-11 04:30:11	announced
2	2024-10-22 05:18:51	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Macrophage

phagosome, Staphylococcus aureus

TPL-2

V-ATPase

Matthias Trost
contact affiliation	Newcastle University Biosciences Institute, Newcastle University, Newcastle upon Tyne, NE24HH, United Kingdom
contact email	matthias.trost@newcastle.ac.uk
lab head
Matthias Trost
contact affiliation	Newcastle University
contact email	matthias.trost@ncl.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD020401
     1. Label: PRIDE project
     2. Name: TPL-2 kinase induces phagosome acidification to promote macrophage killing of Staphylococcus aureus