PXD020247-1

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	2021-03-24
AnnouncementXML	Submission_2021-03-24_06:07:22.666.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: bacteria, DMXL1, macrophage, phagosome, Staphylococcus aureus, TPL-2, V-ATPase

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

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PRIDE project URI

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