Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA305161 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Human peripheral blood T cells (total CD3+) were stimulated for 12 and 24 h with plate bound CD3/CD28 or CD3/CD63 mAbs in the presence or absence of the D2-domain of the cytoplasmic tail of CD45. Total RNA was purified and gene expression profiles were obtained.
2016-02-01 | GSE75723 | GEO
Project description:IgG cytoplasmic tail interferes with the induction of antigen-response genes Experiment Overall Design: Comparing antigen-induced genes between B cells expressing anti-HEL IgM BCR and IgMG BCR (chimeric receptor where the extracellular spacer, transmembrane, and cytoplasmic domain of IgM are replaced with those of IgG1)
2008-06-15 | E-GEOD-7218 | biostudies-arrayexpress
Project description:The GPIbα cytoplasmic tail peptide MPαC was used to study the role of GPIbα in platelet activation.
2024-04-02 | PXD051165 |
Project description:ADAM17 is a cell surface protease that controls the release of the ectodomains of signalling proteins including EGFR ligands and the primary inflammatory cytokine TNF. Reflecting this important role in signalling, dysregulated ADAM17 activity is linked to many human diseases including immunodeficiency, inflammatory bowel disease (IBD), rheumatic arthritis, cancer, and Alzheimer’s disease. iRhom2, a pseudoprotease of the rhomboid-like superfamily, has evolved to be a multifunctional regulatory co-factor of ADAM17. Recent structural and functional work has begun to reveal how the iRhom2 transmembrane and extracellular domains act to control ADAM17 activity. The cytoplasmic domain, however, remains less explored. Here, using a combination of proteomic, genetic and biochemical approaches, we report three distinct mechanisms by which the cytoplasmic domain of iRhom2 contributes to ADAM17 regulation. First, upon oncogenic KRAS signalling, the serine/threonine kinase RSK2 is recruited to the iRhom2 cytoplasmic N-terminus, and coordinates with phosphorylated ERK to mediate the activation of ADAM17. Second, we show that iRhom2 may have an inhibitory function on ADAM17 at the cell surface: stabilising iRhom2 at cell surface by overexpressing iRhom2’s cytoplasmic binding partner, FRMD8, inhibits PMA-stimulated ADAM17 activity. Third, we have identified a previously undefined motif (RKR) in the iRhom2 cytoplasmic domain that represses unstimulated ADAM17 activity. Overall, these findings reveal the complex regulatory system by which the iRhom2 cytoplasmic tail transduces cellular signals to regulate ADAM17 activation, potentially paving the way towards understanding and possibly manipulating the iRhom2/ADAM17 complex in health and disease.
2025-10-20 | PXD063983 | Pride
Project description:Transcriptional effects of soluble CD40 ligand on human naïve B cells
| PRJNA338769 | ENA
Project description:Transcriptional effects of soluble CD40 ligand on human immature dendritic cells
| PRJNA338768 | ENA
Project description:Integrins, the principal extracellular matrix (ECM) receptors of the cell, promote cell adhesion, migration, and proliferation, which are key events for cancer growth and metastasis. To date, most integrin-targeted cancer therapeutics have disrupted integrin-ECM interactions, which are viewed as critical for integrin functions. However, such agents have failed to improve cancer patient outcomes. We show that integrin b1, a highly expressed subunit in lung epithelium, is required for lung adenocarcinoma development in a carcinogen-induced mouse model. Likewise, human lung adenocarcinoma cell lines with integrin b1 deletion failed to form colonies in soft agar and tumors in mice. Mechanistically, we demonstrate that these effects do not require integrin b1-mediated adhesion to ECM but are dependent on integrin b1 cytoplasmic tail-mediated activation of focal adhesion kinase (FAK). Together, these studies support a critical role for integrin b1 in lung tumorigenesis that is mediated through constitutive, ECM-binding independent signaling involving the cytoplasmic tail.
2022-08-01 | GSE175687 | GEO
Project description:The role of cells of the hematopoietic lineage in fibrosis is controversial. Here we evaluate the contribution of Col I+/CD45+ cells (fibrocytes) to lung fibrosis. Systemic bleomycin treatment was used to induce fibrosis in a bone marrow transplant and two transgenic mouse models. Lung cells from these mice were analyzed by flow cytometry, both immediately upon release from the tissue or following growth on tissue-culture plastic. Fibrotic and control human lung tissue were also used. Fibroblasts and fibrocytes derived from a transgenic mouse model were compared in terms of their morphology, growth, and adhesion to fibronectin. Single cell RNAseq was performed with the analysis focusing on CD45-/Col I+ “fibroblasts” and CD45+/Col I+ “fibrocytes” in control and fibrotic mouse lung tissue. Finally, we inhibited fibrosis in mice using a novel, water-soluble version of caveolin scaffolding domain (CSD) called WCSD.
2025-02-26 | GSE259367 | GEO
Project description:Human p97/VCP is a vital AAA ATPase (ATPase associated with diverse cellular activity) plays critical roles in autophagy, endosomal trafficking, and the ubiquitin-proteasome system. Mutations in p97 cause inclusion body myopathy associated with paget’s disease of bone and frontotemporal dementia. P97 is overexpressed in several cancers. The selective active site inhibitor CB-5083 targets p97’s D2 domain and shows potential as an anti-cancer therapeutic, though it has faced clinical setbacks due to off-target effects. To investigate the protein levels changed of HL60 cells (acute myeloid leukemia cell line) by CB-5083 in cytoplasmic, nuclear, and insoluble membrane compartments, we employed fractionation and label-free proteomic analysis. Results reveal distinct compartment-specific protein regulation, providing insight into CB5083’s cellular mechanisms and potential for more targeted therapeutic applications.
2025-05-07 | PXD056029 | Pride
Project description:Kindlin-1, -2, and -3, directly bind integrin β cytoplasmic tails to regulate integrin activation and signaling. Despite their functional significance and link to several diseases, structural information on full-length kindlin proteins remains unknown. Here, we report the crystal structure of human full-length kindlin-3, which reveals a novel homotrimer state. Unlike kindlin-3 monomer, which is the major population in insect and mammalian cell expression systems, kindlin-3 trimer does not bind integrin β cytoplasmic tail as the integrin-binding pocket in the F3 sub-domain of one protomer is occluded by the PH domain of another protomer, suggesting that kindlin-3 is auto-inhibited upon trimer formation. This is also supported by functional assays in which kindlin-3 knockout K562 erythroleukemia cells re-constituted with the mutant kindlin-3 containing trimer-disrupting mutations exhibited an increase in integrin-mediated adhesion and spreading on fibronectin compared to those re-constituted with wild type kindlin-3. Taken together, our findings reveal a novel mechanism of kindlin auto-inhibition that involves its homotrimer formation.
2020-06-08 | PXD019110 | Pride