Ontology highlight
ABSTRACT:
PROVIDER: PRJNA526248 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8701050.fastq.gz | Fastqsanger.gz | |||
| SRR8701060.fastq.gz | Fastqsanger.gz | |||
| SRR8701051.fastq.gz | Fastqsanger.gz | |||
| SRR8701052.fastq.gz | Fastqsanger.gz | |||
| SRR8701053.fastq.gz | Fastqsanger.gz |
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Project description:The multifunctional scaffolding protein β-arrestin-1 plays a vital role in mediating the proliferative effects of nicotine through nAChR signaling. β-arrestins were initially known as negative regulators of GPCR mediated signaling as they promote internalization and desensitization of GPCRs. However, new roles of β-arrestins in receptor trafficking and signaling have been discovered in recent years. They are known to regulate signaling through a number of receptors such as Notch, endothelin A receptor, frizzled, smoothened and the nicotinic cholinergic receptors. Studies from our lab revealed that nAChR signaling induces the translocation of β-arrestin-1 to the nucleus, in a Src dependent manner, where it directly binds to the proliferative E2Fs. Furthermore, the nuclear translocation of β-arrestin-1 results in recruitment of p300 to E2F1 regulated proliferative promoters facilitating histone acetylation and transcription of these promoters. Given the role of β-arrestin-1 in nicotine induced gene expression, we attempted to explore the global association of β-arrestin-1 to the genomic regions upon nicotine stimulation by ChIP sequencing. It was found that β-arrestin-1 is recruited on the promoters of many genes that regulate EMT as well as other regulatory pathways. In this assay, β-arrestin-1 was found to be associated with the promoter regions of genes such as ZNF768, ZNF131, CSF3R, HMGA2, TAL1, RCC1, NKX2-4 etc in response to nicotine stimulation.
2013-12-16 | GSE40689 | GEO
Project description:We found that β-arrestin 1 -/- mice were more sensitive to hypoxia-induced pulmonary arterial hypertension with increased right ventricle hypertrophy and higher right ventricle systolic pressure, while β-arrestin 2 -/- mice developed right ventricle hypertrophy comparable to wild type mice. Moreover, β-arrestin 1 -/- mice had worse right ventricle function than wild type mice in response to chronic hypoxia, whereas β-arrestin 2 -/- mice relatively preserved right ventricle function compared to wild type mice. To investigate the molecular mechanisms responsible for the worse PAH in β-arrestin 1 -/- mice, we performed lung transcriptome analysis of wild type, β-arrestin 1 -/-, and β-arrestin 2 -/- mice using high-throughput RNA-seq.
2018-11-19 | GSE110131 | GEO
Project description:Virus infection may induce excessive interferon (IFN) responses that can lead to host tissue injury or even death. β-arrestin 2 regulates multiple cellular events through the G protein-coupled receptor (GPCR) signaling pathways. Here we demonstrate that β-arrestin 2 also promotes virus-induced production of IFN-β and clearance of viruses in macrophages. β-arrestin 2 interacts with cyclic GMP-AMP synthase (cGAS) and increases the binding of dsDNA to cGAS to enhance cyclic GMP-AMP (cGAMP) production and the downstreatm stimulator of interferon genes (STING) and innate immune responses. Mechanistically, deacetylation of β-arrestin 2 at Lys171 facilitates the activation of the cGAS–STING signaling and the production of IFN-β. In vitro, viral infection induces the degradation of β-arrestin 2 to facilitate immune evasion, while a β-blocker, carvedilol, rescues β-arrestin 2 expression to maintain the antiviral immune response. Our results thus identify a viral immune-evasion pathway via the degradation of β-arrestin 2, and also hint that carvedilol, approved for treating heart failure, can potentially be repurposed as an antiviral drug candidate.
2020-10-22 | GSE159735 | GEO
Project description:The multifunctional scaffolding protein M-NM-2-arrestin-1 plays a vital role in mediating the proliferative effects of nicotine through nAChR signaling. M-NM-2-arrestins were initially known as negative regulators of GPCR mediated signaling as they promote internalization and desensitization of GPCRs. However, new roles of M-NM-2-arrestins in receptor trafficking and signaling have been discovered in recent years. They are known to regulate signaling through a number of receptors such as Notch, endothelin A receptor, frizzled, smoothened and the nicotinic cholinergic receptors. Studies from our lab revealed that nAChR signaling induces the translocation of M-NM-2-arrestin-1 to the nucleus, in a Src dependent manner, where it directly binds to the proliferative E2Fs. Furthermore, the nuclear translocation of M-NM-2-arrestin-1 results in recruitment of p300 to E2F1 regulated proliferative promoters facilitating histone acetylation and transcription of these promoters. Given the role of M-NM-2-arrestin-1 in nicotine induced gene expression, we attempted to explore the global association of M-NM-2-arrestin-1 to the genomic regions upon nicotine stimulation by ChIP sequencing. It was found that M-NM-2-arrestin-1 is recruited on the promoters of many genes that regulate EMT as well as other regulatory pathways. In this assay, M-NM-2-arrestin-1 was found to be associated with the promoter regions of genes such as ZNF768, ZNF131, CSF3R, HMGA2, TAL1, RCC1, NKX2-4 etc in response to nicotine stimulation. Serum starved/quiescent A549 cells and Nicotine stimulated A549 cells
2013-12-16 | E-GEOD-40689 | biostudies-arrayexpress
Project description:Nathaniel L. Coggins, Danielle Trakimas, S. Laura Chang, Anna Ehrlich, Paramita Ray, Kathryn E. Luker, Jennifer J. Linderman & Gary D. Luker. CXCR7 controls competition for recruitment of β-arrestin 2 in cells expressing both CXCR4 and CXCR7. PLoS ONE 9, 6 (2014).
Chemokine CXCL12 promotes growth and metastasis of more than 20 different human cancers, as well as pathogenesis of other common diseases. CXCL12 binds two different receptors, CXCR4 and CXCR7, both of which recruit and signal through the cytosolic adapter protein β-arrestin 2. Differences in CXCL12-dependent recruitment of β-arrestin 2 in cells expressing one or both receptors remain poorly defined. To quantitatively investigate parameters controlling association of β-arrestin 2 with CXCR4 or CXCR7 in cells co-expressing both receptors, we used a systems biology approach combining real-time, multi-spectral luciferase complementation imaging with computational modeling. Cells expressing only CXCR4 maintain low basal association with β-arrestin 2, and CXCL12 induces a rapid, transient increase in this interaction. In contrast, cells expressing only CXCR7 have higher basal association with β-arrestin 2 and exhibit more gradual, prolonged recruitment of β-arrestin 2 in response to CXCL12. We developed and fit a data-driven computational model for association of either CXCR4 or CXCR7 with β-arrestin 2 in cells expressing only one type of receptor. We then experimentally validated model predictions that co-expression of CXCR4 and CXCR7 on the same cell substantially decreases both the magnitude and duration of CXCL12-regulated recruitment of β-arrestin 2 to CXCR4. Co-expression of both receptors on the same cell only minimally alters recruitment of β-arrestin 2 to CXCR7. In silico experiments also identified β-arrestin 2 as a limiting factor in cells expressing both receptors, establishing that CXCR7 wins the "competition" with CXCR4 for CXCL12 and recruitment of β-arrestin 2. These results reveal how competition for β-arrestin 2 controls integrated responses to CXCL12 in cells expressing both CXCR4 and CXCR7. These results advance understanding of normal and pathologic functions of CXCL12, which is critical for developing effective strategies to target these pathways therapeutically.
2024-09-02 | BIOMD0000000599 | BioModels
Project description:The role of nuclear signaling by β2-adrenergic receptor (β2AR) through β-arrestins in the absence of a functional Gαs protein has not been evaluated. This has prevented a comprehensive understanding of the relative contribution of Gαs and β-arrestins to the overall β2AR signaling, thereby limiting our appreciation of how β-arrestin- or Gαs-biased ligands may affect their therapeutic outcomes. To explore the role of Gαs and β-arrestin in nuclear transcriptional programs in a global unbiased approach, we performed RNA sequencing studies in cells lacking either of these two signaling arms downstream from β2AR, followed by detailed bioinformatics analysis of gene expression signatures. We noticed multiple genes whose individual expression levels were distinct in β-arrestin1/2 and Gαs KO cells. Rather than focusing on the individual gene level, we performed a detailed analysis of gene signatures taking advantage of large datasets that were recently compiled as part of the Molecular Signatures Database (MSigDB). This approach supported that β-arrestins are not required for the activation of PKA gene signatures, including prior datasets of forskolin and CREB1 targets, while Gαs is essential. β2AR activation also led to significant changes in multiple MAPK signatures, which clearly support the activation of MAPK nuclear transcriptional programs by these receptors. Although individual variations do exist reflecting the complexities of β-arrestin- and Gαs-mediated signaling events, stimulation of these MAPK regulated gene signatures was not significantly reduced in β-arrestin1/2 KO cells but abolished in Gαs KO cells.
2023-10-17 | GSE245270 | GEO
Project description:Lung cancer remains the leading cause of cancer-related deaths worldwide. M-NM-2-arrestin-1 (ARRB1), a scaffolding protein involved in the termination or desensitization of signals arising from activated G-protein-coupled receptors (GPCRs) has been shown to play a role in invasion and proliferation of many cancers, including nicotine-induced proliferation of human nonM-bM-^@M-^Ssmall cell lung cancers (NSCLCs). In this study, we analyzed nicotine induced and M-NM-2-arrestin-1 dependent genes from the microarray data. Our analysis show that SCF (Stem cell factor) strongly differentiated smokers from non-smokers implying an important role of this gene in NSCLCs. SCF, a major cytokine is the ligand for the c-Kit proto-oncogene. Here we elucidate the molecular mechanisms by which nicotine as well as EGF induces the expression of SCF in lung adenocarcinoma cell lines A549 and H1650. ChIP assays and transient transfection experiments showed that transcription factor E2F1 can positively regulate SCF expression at the transcriptional level; depletion of E2F1 or M-NM-2-arrestin-1 prevented the nicotine-mediated induction of SCF. Given that the binding of SCF to c-Kit leads to activation of multiple downstream signaling pathways including Src, PI3K, MEK and EGFR pathways, our data suggest that the SCF plays a central role in lung carcinogenesis, and may be a potential therapeutic target for combating NSCLC. Studies presented here also provide evidence that SCF along with nicotine promotes self-renewal and proliferation of lung cancer stem cells (CSCs). Our findings reveal an important role and prognostic significance of SCF that can serve as a novel prognostic and predictive biomarker for NSCLC. Transfection of A549 cell line with control siRNA, Beta arrestin siRNA and then stimulation of nicotine
2013-11-10 | E-GEOD-44617 | biostudies-arrayexpress
Project description:Activation of ERK1 and ERK2 is essential in regulation of a wide variety of cellular and physiological processes. In native inner medullary collecting ducts, vasopressin (AVP) working through the V2 subtype vasopressin receptor (V2R)-mediated activation of Gαs, inhibits ERK1 and ERK2 activity. However, it has been reported that V2R can signal independently of Gαs through the activation of β-arrestin, which activates ERK1 and ERK2. Vaptans, V2R antagonists that function as so-called “inverse agonists”, have the potential of promoting cell proliferation via β-arrestin-dependent ERK activation. Here we use the mpkCCD cell line which natively expresses V2R to investigate the effects of AVP, the V2-selective analog dDAVP, and tolvaptan on ERK1 and ERK2 phosphorylation and activation. We demonstrated that ERK1 and ERK2 phosphorylation in mpkCCD cells was significantly reduced by either AVP or dDAVP, in contrast to the increases seen in non-collecting duct cells overexpressing V2R. We also found that tolvaptan has a strong effect to increase ERK1 and ERK2 phosphorylation in the presence of dDAVP and that the tolvaptan effect to increase ERK1 and ERK2 phosphorylation is absent in PKA-null mpkCCD cells. Thus, it appears that the tolvaptan effect to increase ERK activation is PKA-dependent and, therefore, not mediated by the β-arrestin pathway. Overall, the studies show that AVP decreases and that tolvaptan increases ERK1 and ERK2 activation in cells expressing V2R at endogenous levels, and provide no evidence for a role for β-arrestin in the regulation of ERK1 and ERK2 activity.
2024-09-22 | GSE235936 | GEO
Project description:Activation of ERK1 and ERK2 is essential in regulation of a wide variety of cellular and physiological processes. In native inner medullary collecting ducts, vasopressin (AVP) working through the V2 subtype vasopressin receptor (V2R)-mediated activation of Gαs, inhibits ERK1 and ERK2 activity. However, it has been reported that V2R can signal independently of Gαs through the activation of β-arrestin, which activates ERK1 and ERK2. Vaptans, V2R antagonists that function as so-called “inverse agonists”, have the potential of promoting cell proliferation via β-arrestin-dependent ERK activation. Here we use the mpkCCD cell line which natively expresses V2R to investigate the effects of AVP, the V2-selective analog dDAVP, and tolvaptan on ERK1 and ERK2 phosphorylation and activation. We demonstrated that ERK1 and ERK2 phosphorylation in mpkCCD cells was significantly reduced by either AVP or dDAVP, in contrast to the increases seen in non-collecting duct cells overexpressing V2R. We also found that tolvaptan has a strong effect to increase ERK1 and ERK2 phosphorylation in the presence of dDAVP and that the tolvaptan effect to increase ERK1 and ERK2 phosphorylation is absent in PKA-null mpkCCD cells. Thus, it appears that the tolvaptan effect to increase ERK activation is PKA-dependent and, therefore, not mediated by the β-arrestin pathway. Overall, the studies show that AVP decreases and that tolvaptan increases ERK1 and ERK2 activation in cells expressing V2R at endogenous levels, and provide no evidence for a role for β-arrestin in the regulation of ERK1 and ERK2 activity.
2023-11-17 | GSE243773 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE24575: Beta-arrestin-2 deficiency effect on intestinal tumorigenesis in Apc-mutated mice GSE24576: Gene expression analysis of tumors from ApcD14/+ mice Refer to individual Series
2012-01-20 | E-GEOD-24577 | biostudies-arrayexpress