ERK2-dependent gene expression
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE124947 | GEO | 2019/01/11
REPOSITORIES: GEO
Similar Datasets
Project description:ERK2-dependent gene expression
| PRJNA514405 | ENA
Project description:Effective immune responses depend upon appropriate T cell differentiation in accord with the nature of an infectious agent, and the contingency of differentiation depends minimally on T cell antigen receptor, co-receptor, and cytokine signals. In this reverse genetic study we show that the Map Kinase, Erk2, is nonessential for T cell proliferation in the presence of optimum co-stimulation. Instead, it has opposite polar effects on T-bet and Gata3 expression and hence on Th1 and Th2 differentiation. Alternatively, in the presence of TGFbeta, the Erk pathway suppresses a large program of gene expression effectively limiting the differentiation of Foxp3+ T reg cells. In the latter case, the mechanisms involved include suppression of Gata3 and Foxp3, induction of Tbx21, phosphorylation of Smad2,3, and possibly suppression of Socs2, a positive inducer of Stat5 signaling. Consequently, loss of Erk2 severely impeded Th1 differentiation while enhancing the development of Foxp3+ induced T regulatory cells. Selected profiles of gene expression under multiple conditions of T cell activation illustrate the opposing consequences of Erk pathway signaling. Analysis of the Th1 and iTreg differentiation regulated by Erk2. Total RNA obtained from WT or Erk2 deficient CD4 T cells in different conditions.
2012-06-30 | E-GEOD-37554 | biostudies-arrayexpress
Project description:The present study is aimed at detecting and measuring mRNA levels of genes involved in epithelial to mesenchymal transition (EMT) in biological samples, i.e. in peripheral blood samples of colorectal cancer (CRC) patients and healthy controls, to determine the presence of disease, its progression and risk of recurrence.
| 2334276 | ecrin-mdr-crc
Project description:The ERK/MAPK signal transduction cascade is one of the key pathways regulating proliferation and differentiation in development and disease. In human embryonic stem cells (hESCs), ERK signaling is required for their self-renewing property. Here we studied the convergence of the ERK signaling cascade at the DNA by mapping genome-wide kinase-chromatin interactions for ERK2 in hESCs. We observe that ERK2 targets genes coding for small RNAs, histones, and genes involved in cellular metabolism and cell cycle. We find that the transcription factor ELK1 is essential in hESCs and that ERK2 co-occupies promoters bound by ELK1. Strikingly, promoters bound by ELK1 without ERK2 are occupied by Polycomb group proteins that repress genes involved in lineage commitment. In summary, we propose a model where extracellular signaling-stimulated proliferation and intrinsic repression of differentiation is integrated to maintain the identity of hESCs.
2013-05-31 | E-MTAB-1565 | biostudies-arrayexpress
Project description:The overall goal of this project is to investigate the role of Erk2-mediated signaling in regulating the cellular metabolism of cranial neural crest (CNC) cells during palate development. Here, we conducted gene expression profiling of palate tissue from wild type mice as well as those with a neural crest specific conditional inactivation of the Erk2 gene. The latter mice exhibit micrognathia, tongue defects and cleft palate, which is among the most common congenital birth defects and observed in many syndromic conditions. To investigate the adverse effects of dysfunctional ERK signaling on the cellular metabolism of palatal mesenchyme during palatogenesis, we analyzed mice with a neural crest cell-specific conditional inactivation of Erk2 (Erk2fl/fl;Wnt1-Cre). We performed microarray analyses of primary mouse embryonic palatal mesenchymal cells of Erk2fl/fl;Wnt1-Cre mutant mice and Erk2fl/fl control mice, collected at embryonic day 13.5 (n=3 per genotype) and E14.5 (n=5 per genotype).
2015-12-11 | E-GEOD-67087 | biostudies-arrayexpress
Project description:The ERK/MAPK signal transduction cascade is one of the key pathways regulating proliferation and differentiation in development and disease. In human embryonic stem cells (hESCs), ERK signaling is required for their self-renewing property. Here we studied the convergence of the ERK signaling cascade at the DNA by mapping genome-wide kinase-chromatin interactions for ERK2 in hESCs. We observe that ERK2 targets genes coding for small RNAs, histones, and genes involved in cellular metabolism and cell cycle. We find that the transcription factor ELK1 is essential in hESCs and that ERK2 co-occupies promoters bound by ELK1. Strikingly, promoters bound by ELK1 without ERK2 are occupied by Polycomb group proteins that repress genes involved in lineage commitment. In summary, we propose a model where extracellular signaling-stimulated proliferation and intrinsic repression of differentiation is integrated to maintain the identity of hESCs.
2013-05-31 | E-MTAB-1583 | biostudies-arrayexpress
Project description:Hydrogen deuterium exchange mass spectrometry data of the ERK2-RSK2 and ERK2-RSK2-ORF45 complexes. The noncatalytic viral protein ORF45 reconfigures ERK-RSK signaling in cells. This dataset identifies the ORF45-RSK2 interface.
2021-12-22 | MSV000088607 | MassIVE
Project description:The protein kinase ERK2 is recurrently mutated in human squamous cell carcinomas and other tumors. ERK2 mutations cluster in an essential docking recruitment site that interacts with short linear motifs found within intrinsically disordered regions of ERK substrates and regulators. Cancer-associated mutations do not disrupt ERK2 docking interactions altogether but selectively inhibit some interactions while sparing others. However, the full scope of disrupted or maintained interactions remains unknown, limiting our understanding of how these mutations contribute to cancer. We recently defined the docking interactome of wild-type ERK2 by screening a yeast two-hybrid library of proteomic short linear motifs. Here, we apply this approach to the two most recurrent cancer-associated mutants. We find that most sequences binding to WT ERK2 also interact with both mutant forms. Analysis of differentially interacting sequences revealed that ERK2 mutants selectively lose the ability to bind sequences conforming to a specific motif. We solved the co-crystal structure of ERK2 in complex with a peptide fragment of ISG20, a screening hit that binds exclusively to the WT kinase. This co-crystal structure demonstrates the mechanism by which cancer hotspot mutations at Glu81, Arg135, Asp321, and Glu322 selectively impact peptide binding. Finally, we found that cancer-associated ERK2 mutations had a decreased ability to phosphorylate GEF-H1/ARHGEF2, a known ERK substrate harboring a WT-selective docking motif. Collectively, our studies provide a structural rationale for how a broad set of interactions are disrupted by ERK2 hotspot mutations, suggesting mechanisms for pathway rewiring in cancers harboring these mutations.
2025-03-20 | GSE286340 | GEO
Project description:The series of events that allows for the conversion of adherent epithelial cells into migratory cells is collectively known as epithelial-mesenchymal transition (EMT). EMT is involved in triggering neural crest migration during development and in the pathogenesis of diseases, such as cancer metastasis. Whereas Erk signalling is known to be essential for EMT, its influence on the epigenetic and transcriptional programme underlying EMT is poorly understood. Here, using a comprehensive genome-wide analysis of H3K27ac mark and gene expression in primary mammary epithelial cells undergoing EMT, we found that Erk signalling is essential for the epigenetic reprogramming underlying hallmark gene expression and phenotypic changes of EMT. We found that the chemical inhibition of Erk signalling during EMT prevents loss and gain of H3K27ac mark at regulatory regions of epithelial and mesenchymal genes, respectively, and results in a transcriptome and epigenome closer to those of epithelial cells. Further computational analyses identified a distinct set of transcription factor motifs enriched at distal regulatory regions that are epigenetically remodelled by Erk signalling. Altogether, our study reveal an Erk-dependent epigenetic remodelling of distal regulatory elements that results in a gene expression programme that is essential for driving EMT.
2017-06-13 | GSE92333 | GEO
Project description:Effective immune responses depend upon appropriate T cell differentiation in accord with the nature of an infectious agent, and the contingency of differentiation depends minimally on T cell antigen receptor, co-receptor, and cytokine signals. In this reverse genetic study we show that the Map Kinase, Erk2, is nonessential for T cell proliferation in the presence of optimum co-stimulation. Instead, it has opposite polar effects on T-bet and Gata3 expression and hence on Th1 and Th2 differentiation. Alternatively, in the presence of TGFbeta, the Erk pathway suppresses a large program of gene expression effectively limiting the differentiation of Foxp3+ T reg cells. In the latter case, the mechanisms involved include suppression of Gata3 and Foxp3, induction of Tbx21, phosphorylation of Smad2,3, and possibly suppression of Socs2, a positive inducer of Stat5 signaling. Consequently, loss of Erk2 severely impeded Th1 differentiation while enhancing the development of Foxp3+ induced T regulatory cells. Selected profiles of gene expression under multiple conditions of T cell activation illustrate the opposing consequences of Erk pathway signaling.
2012-07-01 | GSE37554 | GEO