PXD020247

PXD020247 is an original dataset announced via ProteomeXchange.

Title	TPL-2 kinase induces phagosome acidification to promote macrophage killing of bacteria
Description	Tumor Progression Locus 2 (TPL-2) kinase mediates Toll-like Receptor (TLR) activation of ERK1/2 and p38 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 critical regulator of V-ATPases, to induce phagosome acidification. Consistent with these results, TPL-2 catalytic activity was required for phagosome maturation 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 V-ATPase induction of phagosome maturation.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:20:18.243.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Helen Flynn
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-07 16:28:44	ID requested
1	2021-03-24 06:07:23	announced
⏵ 2	2024-10-22 05:20:18	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: macrophage,bacteria, TPL-2, V-ATPase, Staphylococcus aureus, DMXL1, phagosome

Bram Snijders
contact affiliation	Mass Spectrometry Proteomics STP The Francis Crick Institute 1 Midland Road London NW1 1AT UK
contact email	bram.snijders@crick.ac.uk
lab head
Helen Flynn
contact affiliation	The Francis Crick Institute
contact email	helen.flynn@crick.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/03/PXD020247

PRIDE project URI

• PRIDE
  1. PXD020247
     1. Label: PRIDE project
     2. Name: TPL-2 kinase induces phagosome acidification to promote macrophage killing of bacteria