PXD020401 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_05:18:50.780.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; deamidated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
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. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Macrophage |
phagosome, Staphylococcus aureus |
TPL-2 |
V-ATPase |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD020401
- Label: PRIDE project
- Name: TPL-2 kinase induces phagosome acidification to promote macrophage killing of Staphylococcus aureus