PXD013840

PXD013840 is an original dataset announced via ProteomeXchange.

Title	Phosphoproteomic analysis of CD2 signaling reveals an AMPK-dependent targeted granule secretion in human cytotoxic T cells
Description	The in-depth analysis of co-stimulatory signaling enhancing the activity of cytotoxic T cells represents a major approach towards the development of immunotherapies. Here we describe that CD2 co-stimulation plays a critical role in the functioning of human cytotoxic T cells (CTLs). We found that CD2 promotes the formation of functional immune synapses by orchestrating the polarization of lytic granules towards the synaptic interface. To broadly explore the CD2 signaling network, we undertook an analysis of protein phosphorylation in CD2-stimulated CTLs, which revealed 549 unique CD2-regulated phosphorylation events in 373 proteins. CD2 stimulation elicited an intricated network of signaling events participating in the regulation of T cell metabolism, vesicular trafficking, autophagy, cell polarity and cytoskeleton organization. We further show that a functionally critical node of this network is the AMP-activated protein kinase (AMPK), which regulates granule polarization at the CTL synapse. Polarized trafficking of granules is driven by the concerted action of TAK1/LKB1/CamKK2 kinases, which locally activate AMPK enriched on CTL lysosome membranes, illustrating a novel functional cross-talk between vesicular compartments in CTLs. Our results thus establish CD2 signaling as key for regulating targeted granule secretion in CTLs and reveal an AMPK-dependent mechanism to explain how AMPK-activating drugs boost anti-tumour CTL activity.
HostingRepository	PRIDE
AnnounceDate	2020-04-28
AnnouncementXML	Submission_2020-07-15_00:47:48.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Roman Fischer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2019-05-14 05:42:35	ID requested
1	2020-04-28 04:26:45	announced
⏵ 2	2020-07-15 00:47:49	announced	2020-07-15: Updated publication reference for PubMed record(s): 32398348.

Zurli V, Montecchi T, Heilig R, Poschke I, Volkmar M, Wimmer G, Boncompagni G, Turacchio G, D'Elios MM, Campoccia G, Resta N, Offringa R, Fischer R, Acuto O, Baldari CT, Kabanova A, Phosphoproteomics of CD2 signaling reveals AMPK-dependent regulation of lytic granule polarization in cytotoxic T cells. Sci Signal, 13(631):(2020) [pubmed]

submitter keyword: CD2, phosphoproteome, granule secretion

Roman Fischer
contact affiliation	Discovery Proteomics Facility University of Oxford
contact email	roman.fischer@ndm.ox.ac.uk
lab head
Roman Fischer
contact affiliation	University of Oxford
contact email	roman.fischer@ndm.ox.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/2020/04/PXD013840

PRIDE project URI

• PRIDE
  1. PXD013840
     1. Label: PRIDE project
     2. Name: Phosphoproteomic analysis of CD2 signaling reveals an AMPK-dependent targeted granule secretion in human cytotoxic T cells