Lung-specific MCEMP1 acts as an adaptor for KIT to promote SCF-mediated mast cell proliferation [PCMC RNA-seq]
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ABSTRACT:
PROVIDER: PRJNA808602 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We analyzed transcriptomic changes in Mcemp1-/- Peritoneal cell-derived mast cells (PCMC) versus Mcemp1 wild-type PCMC cultured with SCF and IL-3 for 9-days.
2023-03-13 | GSE197041 | GEO
Project description:Lung-specific MCEMP1 acts as an adaptor for KIT to promote SCF-mediated mast cell proliferation
| PRJNA808599 | ENA
Project description:Lung-specific MCEMP1 acts as an adaptor for KIT to promote SCF-mediated mast cell proliferation [Lung RNA-seq]
| PRJNA808600 | ENA
Project description:Global phosphoproteomics can reveal signaling cascades in unprecedented detail. The SCF/KIT axis represents a vital hematopoietic receptor tyrosine kinase (RTK) system with gain-of-function mutations prompting the development of mastocytosis and leukemia. Here, we employed a label-free phosphoproteomics profiling strategy to provide the first comprehensive portrayal of SCF-triggered phosphosignaling. Employing untransformed skin-derived mast cells expressing vast amounts of KIT, we uncover around 10,500 class-I-phosphosites following ligand-induced KIT dimerization. Apart from STAT5, the MEK/ERK cascade (including upstream and downstream events) stood out as highly stimulatable by SCF compared to less impacted PI3K/Akt>p38>JNK, a pattern validated by time-resolved immunoblotting. Direct comparison between MEK/ERKÕs and PI3KÕs support of basic programs (anti-apoptosis, cell cycle progression) revealed equipotency with substantial redundancy between the modules. In functional outputs, ERK showed dominance over PI3K regarding cytokine stimulation (TNF-a, IL-8, LIF, OSM) and was the only contributor in the induction of immediate early genes (Fos, JunB, Egr1). Our proteome-wide screen also found Å1,000 phosphosites currently undescribed in databases, pertaining to multiple protein classes. Among candidates, capicua (and components of its network) experienced massive phosphorylation by SCF. Perturbation with capicua by RNA interference unveiled its function as a potent KIT repressor, whose deregulation may contribute to the development of mastocytosis. We demonstrate the utility of an unbiased approach to uncover single protein entities and entire networks activated by RTKs, that can be surveyed experimentally. This rich resource enhances our understanding of RTK-elicited signaling networks and can serve as a benchmark to identify pathological processes, e.g. under circumstances of KIT deregulation.
2022-11-15 | PXD028252 | Pride
Project description:Objective is to identify microRNAs regulated by KIT signaling in mast cells. miRNA profiles of murine bone marrow derived mast cells with and without SCF treatment were compared. In addition, miRNA profiles of the P815 mutant KIT cell line with and without the KIT inhibitor, imatinib, were compared. We identified miRNAs that were differentially regulated by KIT signals.
2011-01-25 | GSE26783 | GEO
Project description:Objective is to identify microRNAs regulated by KIT signaling in mast cells. miRNA profiles of murine bone marrow derived mast cells with and without SCF treatment were compared. In addition, miRNA profiles of the P815 mutant KIT cell line with and without the KIT inhibitor, imatinib, were compared. We identified miRNAs that were differentially regulated by KIT signals. Two systems were used to identify microRNAs regulated by KIT. RNA was collected from primary murine bone marrow derived mast cells (BMMC) treated and not treated with KIT ligand (SCF). In addition, RNA was harvested from the P815 (activating KIT mutation positive) cell line treated and not treated with the KIT inhibitor, imatinib. Samples were harvested after 24 hours of treatment
2011-01-25 | E-GEOD-26783 | biostudies-arrayexpress
Project description:Global phosphoproteomics can reveal signaling cascades in unprecedented detail. The SCF/KIT axis represents a vital hematopoietic receptor tyrosine kinase (RTK) system with gain-of-function mutations prompting the development of mastocytosis and leukemia. Here, we employed a label-free phosphoproteomics profiling strategy to provide the first comprehensive portrayal of SCF-triggered phosphosignaling. Employing untransformed skin-derived mast cells expressing vast amounts of KIT, we uncover around 10,500 class-I-phosphosites following ligand-induced KIT dimerization. Apart from STAT5, the MEK/ERK cascade (including upstream and downstream events) stood out as highly stimulatable by SCF compared to less impacted PI3K/Akt>p38>JNK, a pattern validated by time-resolved immunoblotting. Direct comparison between MEK/ERKÕs and PI3KÕs support of basic programs (anti-apoptosis, cell cycle progression) revealed equipotency with substantial redundancy between the modules. In functional outputs, ERK showed dominance over PI3K regarding cytokine stimulation (TNF-a, IL-8, LIF, OSM) and was the only contributor in the induction of immediate early genes (Fos, JunB, Egr1). Our proteome-wide screen also found Å1,000 phosphosites currently undescribed in databases, pertaining to multiple protein classes. Among candidates, capicua (and components of its network) experienced massive phosphorylation by SCF. Perturbation with capicua by RNA interference unveiled its function as a potent KIT repressor, whose deregulation may contribute to the development of mastocytosis. We demonstrate the utility of an unbiased approach to uncover single protein entities and entire networks activated by RTKs, that can be surveyed experimentally. This rich resource enhances our understanding of RTK-elicited signaling networks and can serve as a benchmark to identify pathological processes, e.g. under circumstances of KIT deregulation.
2022-03-31 | PXD028245 | Pride
Project description:This study evaluates the effects of 72h stimulus with stem cell factor (SCF) (100 ng/mL) and TGF-b (1 ng/mL or 10 ng/mL), both alone and in combination, on the transcriptome of bone marrow-derived cultured mast cells (BMMCs) grown in IL-3 for 6-8 weeks. Through this approach, we find that SCF dramatically enhances TGF-b mediated upregulation of signature genes associated with mucosal mast cells, including transcripts encoding the proteases mMCP-1 (Mcpt1) and mMCP-2 (Mcpt2). Replicates indicate biologic duplicates. Samples were sequenced on an Illumina NextSeq 500.
2020-08-03 | GSE155571 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-03-13 | GSE197042 | GEO
Project description:Activating mutations in the receptor KIT promote the dysregulated proliferation of human mast cells (huMCs). The resulting neoplastic huMCs secrete extracellular vesicles (EVs) that can transfer oncogenic KIT among other cargo into recipient cells. Despite potential contributions to diseases, KIT-containing EVs have not been thoroughly investigated. Here, we isolated KIT-EV subpopulations released by neoplastic huMCs using an immunocapture approach that selectively isolates EVs containing KIT in its proper topology. Proteomic profiling was performed on KIT-containing EVs compared to KIT-depleted EV populations, and on KIT-EVs that are microvesicle- and exosome-like.
2023-03-10 | PXD033889 | Pride