Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Effect of enforced expression of ZAP70 in development of naïve B-cell repertoire

ABSTRACT: Effect of enforced expression of ZAP70 in development of naïve B-cell repertoire

PROVIDER: PRJNA627646 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR11596596_1.fastq.gz	Fastqsanger.gz
	SRR11596596_2.fastq.gz	Fastqsanger.gz
	SRR11596597_1.fastq.gz	Fastqsanger.gz
	SRR11596597_2.fastq.gz	Fastqsanger.gz
	SRR11596598_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 8

Similar Datasets

Effect of enforced expression of ZAP70 in development of naïve B-cell repertoire

Project description:We investigate the effect of altered kinase levels (ZAP70) in the VDJ usage of B-cell receptors in humanized mice

2021-07-07 | GSE149199 | GEO

Lck promotes Zap70-dependent LAT phosphorylation by bridging Zap70 to LAT

Project description:T cell antigen receptor (TCR) signaling depends upon the kinases Lck and Zap70. Lck phosphorylates the TCR, facilitating Zap70 recruitment to the stimulated TCR. Lck also phosphorylates Zap70, relieving its auto-inhibition and activating its catalytic domain. Zap70 then phosphorylates the critical adaptors LAT and SLP76 which serve to nucleate key effector molecules required for downstream responses. However, mechanisms facilitating the interaction of Zap70 with its substrates have not been described. We report an evolutionarily conserved proline-rich motif in LAT is important for Zap70-induced phosphorylation of LAT and downstream signaling. This LAT proline-rich motif associated with the Lck SH3 domain, thereby facilitating Zap70-mediated phosphorylation of LAT and downstream functions. Our results suggest Lck orchestrates multiple steps in TCR signaling including the newly described facilitation of the interaction of Zap70 with its substrate LAT. This previously unrecognized feature of TCR proximal signaling may contribute to the development of more immunomodulatory therapies.

2019-11-12 | PXD008258 | Pride

Developmental partitioning of SYK and ZAP70 prevents autoimmunity and cancer

Project description:Even though SYK and ZAP70 kinases share high sequence homology and serve analogous functions, their expression in B and T cells is strictly segregated throughout evolution. Here, we identified aberrant ZAP70 expression as a common feature in a broad range of B cell malignancies. We validated SYK as the kinase that sets the thresholds for negative selection of autoreactive and premalignant clones. When aberrantly expressed in B cells, ZAP70 competes with SYK at the BCR signalosome and redirects SYK from negative selection to tonic PI3K signaling, thereby promoting B cell survival. In genetic mouse models for B-ALL and B-CLL, conditional expression of Zap70 accelerated disease onset, while genetic deletion impaired malignant transformation. Inducible activation of Zap70 during B cell development compromised negative selection of autoreactive B cells, resulting in pervasive autoantibody production. Strict segregation of the two kinases is critical for normal B cell selection and represents a central safeguard against the development of autoimmune disease and B cell malignancies.

2021-05-21 | GSE148797 | GEO

Comparison of Chronic Lymphocytic Leukemia patients expressing high or low levels of ZAP70 mRNA

Project description:Comparison of Chronic Lymphocytic Leukemia patients expressing high or low levels of ZAP70 mRNA: prognostic factors and interaction with the microenvironment. Zeta-associated protein 70 (ZAP70) is a widely recognized prognostic factor in chronic lymphocytic leukemia (CLL), but mechanisms by which its higher expression leads to a poor outcome remain to be fully explained. In an attempt to unveil unfavorable cellular properties linked to high ZAP70 expression, we used gene expression profiling to identify genes associated with disparities in B-cells from CLL patients expressing high versus low ZAP70 mRNA, measured by quantitative real-time PCR. Keywords: comparison of poor and good prognosis CLL patient transcriptome regarding ZAP70 expression

2009-04-18 | GSE12734 | GEO

Single-cell lineage mapping of a diverse virus-specific naïve CD4 T cell repertoire

Project description:The naïve polyclonal CD4 T cell repertoire can differentiate into multiple lineages during acute viral infection, with some T cell clones exhibiting a preferred lineage choice. TCR α CDR3 motifs can partially influence a clone-intrinsic lineage preference towards TFH fate.

2020-11-10 | GSE158896 | GEO

Transcription profiling of human chronic lymphocytic leukemia patients expressing high or low levels of ZAP70 mRNA

Project description:Comparison of Chronic Lymphocytic Leukemia patients expressing high or low levels of ZAP70 mRNA: prognostic factors and interaction with the microenvironment. Zeta-associated protein 70 (ZAP70) is a widely recognized prognostic factor in chronic lymphocytic leukemia (CLL), but mechanisms by which its higher expression leads to a poor outcome remain to be fully explained. In an attempt to unveil unfavorable cellular properties linked to high ZAP70 expression, we used gene expression profiling to identify genes associated with disparities in B-cells from CLL patients expressing high versus low ZAP70 mRNA, measured by quantitative real-time PCR. Experiment Overall Design: Two groups of seven CLL patients were compared, selected on the basis of either high or low ZAP70 mRNA expression. Total RNA from CD19+ purified cells was exctracted and hybidyzed on Affymetrix GeneChipÃÂ® Human Genome U133 Plus 2.0 Array. Amplification, hybridization and scanning were done according to standard Affymetrix protocols (www.affymetrix.com). CEL files were ,normalized with RMA method.

2009-04-25 | E-GEOD-12734 | biostudies-arrayexpress

Gene expression analysis of Eu-TCL1 CLL cells with Zap70 expression

Project description:RNA-sequencing was used to determine gene expression of 4 Eµ-TCL1 (control) and 4 Eµ-TCL1 Zap70-ki mice which developed CLL.

2021-07-07 | GSE159908 | GEO

Identification of the intermolecular disulfide bonds between NPGPx and ZAP70

Project description:The tyrosine kinase, ζ-chain-associated protein of 70 kDa (ZAP70), is essential for T cell development and activation. However, it remains elusive whether a direct redox regulation affects ZAP70 activity upon TCR stimulation. Here, we showed that deficiency of non-selenocysteine containing phospholipid hydroperoxide glutathione peroxidase (NPGPx), a redox sensor, resulted in T cell hyperproliferation and elevated cytokine productions. Through proteomic approaches, ZAP70 is identified as the key interacting protein of NPGPx through disulfide bonding. Here we utilized the MS/MS spectra to identify the cysteine residues in ZAP70 for NPGPx-mediated regulation. Combined molecular approaches, our results elucidate a delicate redox mechanism that NPGPx serves as a modulator to curb ZAP70 functions in maintaining T cell homeostasis.

2021-01-25 | PXD017034 | Pride

Enforced MAB21L4 expression enhances epidermal diferentiation

Project description:Enforced MAB21L4 expression enhances epidermal diferentiation

| PRJNA788771 | ENA

Altered thymic differentiation and modulation of arthritis by invariant NKT cells expressing mutant ZAP70 [II]

Project description:Various subsets of invariant natural killer T (iNKT) cells with different cytokine productions develop in the mouse thymus, but the factors driving their differentiation remain unclear. Here we show that hypomorphic alleles of Zap70 or chemical inhibition of Zap70 catalysis lead to an increase of IFN-g-producing iNKT cells (NKT1 cells), suggesting NKT1 cells may require a lower TCR signal threshold. Zap70 mutant mice develop IL-17-dependent arthritis. iNKT cells and therapeutic induction of IFN-g secretion by activating iNKT cells are protective in this model, but the representation of IFNg versus IL-17 secreting iNKT cells in the joint change in favor of IL-17 producers as disease worsened. NKT1 cells are also present in the synovial fluid of arthritis patients, where they could be beneficial. Our data therefore suggest that TCR signal strength during thymic differentiation may influence not only IFNg production, but also the protective function of iNKT cells in arthritis.

2018-05-18 | GSE114594 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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