Browse
Submit Data
Databases
API
Help

Dataset Information

436 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Dissection of IL-2 and IL-15 signaling pathways

ABSTRACT: The aim of this study was to compare the signaling cascades initiated by the two closely related cytokines IL-2 and IL-15. Considering the relevance of protein tyrosine phosphorylation in signal transduction, in order to quantify changes in protein phosphorylation in response to IL-2 and IL-15, we combined triple SILAClabeling of leukemic T-cells with phosphotyrosine (pY)-specific antibody-based protein enrichment followed by mass spectrometry (MS) analysis. Following the strategy described above, we managed to decipher in detail the complex signaling networks triggered by IL-2 and IL-15. Interestingly, a large number of components of the three main signaling pathways known to be initiated in response to the interleukins (JAK/STAT; RAS/MAPK; PI3K/AKT) were identified.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): T Cell

DISEASE(S): Acute Leukemia

SUBMITTER: Nerea Osinalde

LAB HEAD: Nerea Osinalde

PROVIDER: PXD001129 | Pride | 2014-09-23

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Publications

Simultaneous dissection and comparison of IL-2 and IL-15 signaling pathways by global quantitative phosphoproteomics.

Osinalde Nerea N Sanchez-Quiles Virginia V Akimov Vyacheslav V Guerra Barbara B Blagoev Blagoy B Kratchmarova Irina I

Proteomics 20140930 2-3

Common γ-chain family of cytokines (IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21, where IL stands for interleukin) are key regulators of the immune homeostasis that exhibit pleiotropic biological activities and even sometimes redundant roles as a result of the utilization of the same receptor subunit. However, they also exert distinct functions that make each of them to be indispensable. For instance, all family members can act as T-cell growth factors; however, we found that IL-15 but not IL-7 can ...[more]

PMID: 25142963

Similar Datasets

Characterization of receptor-associated protein complex assembly in Interleukin (IL)-2- and IL-15-activated T-lymphocytes

Project description:Despite extensive investigation, it remains a paradox that IL-2 and IL-15 can differentially modulate the immune response using the same signaling receptors. In our previous work, we dissected the phosphotyrosine-driven signaling cascades triggered by both cytokines in Kit225 T-cells unveiling subtle differences that may contribute to their functional dichotomy. In the present study, we aimed to decipher the receptor complex assembly in IL-2- and IL-15-activated T-lymphocytes that is fine tune orchestrated by site-specific phosphorylation events. Comparing the cytokine-induced interactome of the interleukin receptor beta and gamma subunits shared by the two cytokines, we defined the components of the early IL-2 and IL-15 receptor-associated complex discovering novel constituents such as FAM59A and SOCS2. Additionally, phosphopeptide-directed analysis allowed us to detect several cytokine-dependent and –independent phosphorylation events within the activated receptor complex including novel phosphorylated sites located in the cytoplasmic region of IL-2Rβ. We proved that the distinct phosphorylations induced by the cytokines serve for recruiting different types of effectors to the initial receptor/ligand complex. Whereas IL-2Rβ pS431 binds to clathrins, which are involved in the receptor internalization and subsequent signal attenuation, IL-2Rγ pY325 and pY357 attract phosphatases, adaptor proteins, kinases as well as the newly identified member of the interleukin receptor complex SOCS2. Overall our study sheds new light into the initial molecular mechanisms triggered by IL-2 and IL-15 and constitutes a further step towards a better understanding of the early signaling aspects of the two closely-related cytokines in T-lymphocytes.

2016-08-08 | PXD002386 | Pride

Nuclear phosphoproteomics analysis of resting and IL-2-stimulated T lymphocytes

Project description:The aim of the present project was to study in detail the site-specific phosphorylation events occurring both in resting as well as in T lymphocytes stimulated with IL-2 for five minutes. For that purpose we combined SILAC-based quantitative mass spectrometry analysis with phosphopeptide enrichment using TiO2 beads. We performed three biological replicas of the same experiment which resulted in the identification of above 8500 unique phosphosites corresponding to more than 3000 proteins. From the 6145 phosphosites that were consistently quantified in at least 2 out of the 3 replicas performed, we detected that 390 were regulated by IL-2 being the up-regulated phosphosites five times more abundant than the down-regulated ones. Those IL-2-dependent phosphosites corresponded to distinct proteins involved in distinct aspects of gene expression and cell cycle regulation.

2016-04-18 | PXD002839 | Pride

Proteome and Secretome Analysis Reveals Differential Post-Transcriptional Regulation of Toll-Like Receptor Responses

Project description:Toll-like receptors (TLRs) are essential sensors in innate immunity and among the first to detect invading pathogens. Many studies of TLR responses have focused on the intracellular signaling events that occur upon receptor stimulation. However, proteins released from the cell play a key role in cell-cell communication during an immune response. We have used mass spectrometry-based proteomic methods to investigate both the intracellular and extracellular responses of macrophages stimulated with individual TLR2, TLR4, and TLR7 ligands and whole pathogens. We performed global quantitative analyses of the mouse macrophage proteome and secretome using stable isotope labeling with amino acids and high-resolution mass spectrometry.

2017-03-06 | PXD004113 | Pride

Phosphoproteome profiling of toll-like receptor response to different ligand stimulation in macrophages identifies differences in global phosphorylation dynamics

Project description:Toll-like receptors are among the first sensors that detect and drive immune responses to pathogens. Macrophages that encounter a pathogen are usually not stimulated through one TLR but by a combination of these receptors engaged by distinct ligands produced by the microbe. As a first step to understanding the integrated signaling under such complex conditions, we have investigated the differences in the phosphoprotein signaling cascades triggered by individual TLR4, TLR2 and TLR7 ligands using a single responding cell population. We performed a global quantitative and early post-stimulation kinetic analysis of the mouse macrophage phosphoproteome using stable isotope labeling with amino acids coupled to phosphopeptide enrichment and high-resolution mass spectrometry.

2014-06-09 | PXD000761 | Pride

Quantitative phosphoproteomics analysis of olfactory receptor signaling in prostate cancer cells

Project description:The olfactory receptor PSGR1 is not only expressed in olfactory tissue but shows expression in the prostate. In addition, the expression of this receptor is elevated in prostate cancer as well as other prostate diseases and can be used as diagnostic marker. The signalling cascade triggered by the activation of this receptor remains largely unknown until now. To investigate PSGR1 signalling, we stimulated the PSGR1 receptor with one of its known ligands, the odorant beta-ionone, and used a phosphoproteomics approach to identify mediators of PSGR1 signalling. We found the non-receptor tyrosine kinase Pyk2, the tumour suppressor NDRG1 as well as the sodium/hydrogen exchanger NHE1 to be downstream targets of activated PSGR1.

2016-07-08 | PXD000985 | Pride

Uncovering structural themes across cilia microtubule inner proteins with implications for human cilia function

Project description:Centrosomes and cilia are microtubule-based superstructures vital for cell division, signaling, and motility. The once thought hollow lumen of their microtubule core structures was recently found to hold a rich meshwork of microtubule inner proteins (MIPs). To address outstanding questions on how distinct MIPs evolved to recognize microtubule inner surfaces, we applied computational sequence analyses, structure predictions, and experimental validation to uncover evolutionarily conserved microtubule- and MIP-binding domains named NWE, PYG, SNYG, ELLEn, and GFG-repeat by their signature motifs. These novel domains intermix with MT-binding DM10-modules and Mn-repeats in 24 Chlamydomonas and 33 human proteins. The domains specialties provided keys to identify elusive cross-species homologs, 11 hitherto unknown human MIP candidates, and functional properties for five protein subfamilies, including the microtubule seam-binding NWE and ELLEn families. Our work demonstrates that MIPs co-evolved with centrosomes and cilia, defines structural innovations that underpin centriole and axoneme assembly, and explain causes of ciliopathies.

2024-03-01 | PXD037582 | Pride

Characterization of LysargiNase for use in phosphoproteomics experiments, partII

Project description:Use of parallel digest with LysargiNase and trypsin to cover complementary phosphosites / characterization of phospho-motifs preferentially identified by each protease

2014-12-16 | PXD001114 | Pride

Dissection of IL-2 and IL-15 signaling pathways

Project description:The aim of this study was to compare the signaling cascades initiated by the two closely related cytokines IL-2 and IL-15. Considering the relevance of protein tyrosine phosphorylation in signal transduction, in order to quantify changes in protein phosphorylation in response to IL-2 and IL-15, we combined triple SILAClabeling of leukemic T-cells with phosphotyrosine (pY)-specific antibody-based protein enrichment followed by mass spectrometry (MS) analysis. Following the strategy described above, we managed to decipher in detail the complex signaling networks triggered by IL-2 and IL-15. Interestingly, a large number of components of the three main signaling pathways known to be initiated in response to the interleukins (JAK/STAT; RAS/MAPK; PI3K/AKT) were identified.

2017-03-29 | MSV000080767 | MassIVE

The Effect of Fatty Acids in Hepatic Insulin Resistance - Part 1

Project description:Monounsaturated fatty acid (MUFA) oleic acid (OA) has been reported to restore saturated fatty acid palmitic acid (PA)-induced hepatic insulin resistance (IR). However, the detailed molecular mechanism remains elusive. In addition, -3 polyunsaturated fatty acid (PUFA) such as Eicosapentaenoic acid (EPA) has also exerted opposite effects to PA in muscle IR. But whether it plays the same role in hepatic IR and the possible mechanism involved needs to be further explored. Here, we compared the proteome change of HepG2 cells after different fatty acids treatment.

2019-07-11 | PXD012065 | Pride

Hypoxia-induced changes in SUMO conjugation affect transcriptional regulation under low oxygen

Project description:Recent data support that sumoylation, the covalent attachment of the Small Ubiquitin-related MOdifier (SUMO) to proteins, is involved in the activation of the hypoxic response and the ensuing signalling cascade. To gain insights into differences of the SUMO1 and SUMO2/3 proteome of HeLa cells under normoxia and cells grown for 48 h under hypoxic conditions, we employed endogenous SUMO-immunoprecipitation in combination with quantitative mass spectrometry (SILAC).

2019-04-03 | PXD010946 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data