ArticleThe Journal of biological chemistry2015
Thrombin promotes sustained signaling and inflammatory gene expression through the CDC25 and Ras-associating domains of phospholipase Cϵ.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Structural insights into Phospholipase Cε activity and regulation.The Journal of biological chemistry · 2026Review
- Thrombin increases the expression of cholesterol 25-hydroxylase in rat astrocytes after spinal cord injury.Neural regeneration research · 2023Article
- KRIT1-mediated regulation of neutrophil adhesion and motility.The FEBS journal · 2023Article
- Phospholipase Cε insufficiency causes ascending aortic aneurysm and dissection.American journal of physiology. Heart and circulatory physiology · 2022Article
- Thrombin acts as inducer of proinflammatory macrophage migration inhibitory factor in astrocytes following rat spinal cord injury.Journal of neuroinflammation · 2022Article
- Thrombin induces morphological and inflammatory astrocytic responses via activation of PAR1 receptor.Cell death discovery · 2022Article
- Thrombin aggravates hypoxia/reoxygenation injury of astrocytes by activating the autophagy pathway mediated by SPRED2.Experimental and therapeutic medicine · 2021Article
- Structure and regulation of phospholipase Cβ and ε at the membrane.Chemistry and physics of lipids · 2021Review
- Functional and structural characterization of allosteric activation of phospholipase Cε by Rap1A.The Journal of biological chemistry · 2020Article
- Structure of phospholipase Cε reveals an integrated RA1 domain and previously unidentified regulatory elements.Communications biology · 2020Article
- Sphingosine 1-phosphate receptor 3 and RhoA signaling mediate inflammatory gene expression in astrocytes.Journal of neuroinflammation · 2017Article
- Phospholipase C-ε signaling mediates endothelial cell inflammation and barrier disruption in acute lung injury.American journal of physiology. Lung cellular and molecular physiology · 2016Article
- Phospholipase Cϵ Activates Nuclear Factor-κB Signaling by Causing Cytoplasmic Localization of Ribosomal S6 Kinase and Facilitating Its Phosphorylation of Inhibitor κB in Colon Epithelial Cells.The Journal of biological chemistry · 2016Article
- Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Phospholipase C-epsilon (PLCϵ) plays a critical role in G-protein-coupled receptor-mediated inflammation. In addition to its ability to generate the second messengers inositol 1,4,5-trisphosphate and diacylglycerol, PLCϵ, unlike the other phospholipase C family members, is activated in a sustained manner. We hypothesized that the ability of PLCϵ to function as a guanine nucleotide exchange factor (GEF) for Rap1 supports sustained downstream signaling via feedback of Rap1 to the enzyme Ras-associating (RA2) domain. Using gene deletion and adenoviral rescue, we demonstrate that both the GEF (CDC25 homology domain) and RA2 domains of PLCϵ are required for long term protein kinase D (PKD) activation and subsequent induction of inflammatory genes. PLCϵ localization is largely intracellular and its compartmentalization could contribute to its sustained activation. Here we show that localization of PLCϵ to the Golgi is required for activation of PKD in this compartment as well as for subsequent induction of inflammatory genes. These data provide a molecular mechanism by which PLCϵ mediates sustained signaling and by which astrocytes mediate pathophysiological inflammatory responses.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.