PXD009513

PXD009513 is an original dataset announced via ProteomeXchange.

Title	Combined phosphoproteome analysis of the response to mycobacterial cord factor reveals a dichotomy of Mincle-dependent and -independent signaling in macrophages
Description	Sensing of Mycobacterium tuberculosis by the immune system relies on recognition by macrophages. Mycobacterial cord factor, trehalose-6,6’-dimycolate (TDM), is the most abundant cell wall glycolipid and binds to the C-type lectin receptor Mincle. To explore the kinase signaling linking the TDM-Mincle interaction to gene expression, we employed quantitative phosphoproteome analysis using dimethyl-labeling and high-resolution mass spectrometry. TDM caused upregulation of 6.7% and suppressed 3.8% of the 14k phospho-sites identified in 3727 proteins. Mincle-dependent phosphorylation was observed for several canonical players of CLR signaling (e.g. PLC, PKC), and was enriched for PKC and GSK3 kinase motifs. Mincle-dependent activation of the PI3K-AKT-GSK3 pathway contributed to TDM-induced inflammatory gene expression and required the PI3K regulatory subunit p85. Unexpectedly, a substantial fraction of TDM-induced phosphorylation was Mincle-independent, a finding which was paralleled by RNAseq-based transcriptome data. GO and pathway enrichment analysis of both datasets concurred in the requirement for Mincle in “innate immune response”. In contrast, Mincle-independent phosphorylation and transcriptome responses to TDM were linked to “cell cycle” and to the DNA damage response. Collectively, our global analyses show substantial reprogramming of macrophages by mycobacterial cord factor and reveal a dichotomy of Mincle-dependent and –independent signaling linked to distinct biological responses
HostingRepository	PRIDE
AnnounceDate	2019-01-17
AnnouncementXML	Submission_2019-01-17_04:21:00.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	phosphorylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2018-04-16 03:51:25	ID requested
⏵ 1	2019-01-17 04:21:01	announced

Hansen M, Peltier J, Killy B, Amin B, Bodendorfer B, H, ä, rtlova A, Uebel S, Bosmann M, Hofmann J, B, ü, ttner C, Ekici AB, Kuttke M, Franzyk H, Foged C, Beer-Hammer S, Schabbauer G, Trost M, Lang R, Macrophage Phosphoproteome Analysis Reveals MINCLE-dependent and -independent Mycobacterial Cord Factor Signaling. Mol Cell Proteomics, 18(4):669-685(2019) [pubmed]

curator keyword: Biological

submitter keyword: Mouse, Macrophages, Dimethyl, Phosphoprotoemic, Mycobacterium tuberculosis

Prof Matthias Trost
contact affiliation	Institute for cell and Molecular biology (ICAMB), Faculty of Medical Sciences, Newcastle University, NewcastleUpon Tyne, UK
contact email	matthias.trost@ncl.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. PXD009513
     1. Label: PRIDE project
     2. Name: Combined phosphoproteome analysis of the response to mycobacterial cord factor reveals a dichotomy of Mincle-dependent and -independent signaling in macrophages