ArticleThe Journal of biological chemistry2006
G-protein-coupled receptor agonists activate endogenous phospholipase Cepsilon and phospholipase Cbeta3 in a temporally distinct manner.
Article in The Journal of biological chemistry, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 83 citations in OpenAlex.
- Structural insights into Phospholipase Cε activity and regulation.The Journal of biological chemistry · 2026Review
- Phospholipase C epsilon 1 as a therapeutic target in cardiovascular diseases.Journal of advanced research · 2025Review
- RhoA allosterically activates phospholipase Cε via its EF hands.Communications biology · 2025Article
- Untangling the role of RhoA in the heart: protective effect and mechanism.Cell death & disease · 2024Review
- PIP5Kγ Mediates PI(4,5)P2/Merlin/LATS1 Signaling Activation and Interplays with Hsc70 in Hippo-YAP Pathway Regulation.International journal of molecular sciences · 2023Article
- Targeting small GTPases: emerging grasps on previously untamable targets, pioneered by KRAS.Signal transduction and targeted therapy · 2023Review
- Dissecting the Mechanism of Action of Spiperone-A Candidate for Drug Repurposing for Colorectal Cancer.Cancers · 2022Article
- Functional and structural characterization of allosteric activation of phospholipase Cε by Rap1A.The Journal of biological chemistry · 2020Article
- Bok regulates mitochondrial fusion and morphology.Cell death and differentiation · 2019Article
- Neuronal and glial DNA methylation and gene expression changes in early epileptogenesis.PloS one · 2019Article
- Phosphatidylinositol 4-phosphate is a major source of GPCR-stimulated phosphoinositide production.Science signaling · 2018Article
- LIM and cysteine-rich domains 1 is required for thrombin-induced smooth muscle cell proliferation and promotes atherogenesis.The Journal of biological chemistry · 2018Article
- Clinical significance of the correlation between PLCE 1 and PRKCA in esophageal inflammation and esophageal carcinoma.Oncotarget · 2017Article
- The controversial role of phospholipase C epsilon (PLCε) in cancer development and progression.Journal of Cancer · 2017Review
- 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
- Knockout of phospholipase Cε attenuates N-butyl-N-(4-hydroxybutyl) nitrosamine-induced bladder tumorigenesis.Molecular medicine reports · 2016Article
- Article
- PLCβ3 mediates cortactin interaction with WAVE2 in MCP1-induced actin polymerization and cell migration.Molecular biology of the cell · 2015Article
- Thrombin promotes sustained signaling and inflammatory gene expression through the CDC25 and Ras-associating domains of phospholipase Cϵ.The Journal of biological chemistry · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Phospholipase Cepsilon (PLCepsilon) is one of the newest members of the phosphatidylinositol-specific phospholipase C (PLC) family. Previous studies have suggested that G-protein-coupled receptors (GPCRs) stimulate phosphoinositide (PI) hydrolysis by activating PLCbeta isoforms through G(q) family G proteins and Gbetagamma subunits. Using RNA interference to knock down PLC isoforms, we demonstrate that the GPCR agonists endothelin (ET-1), lysophosphatidic acid (LPA), and thrombin, acting through endogenous receptors, couple to both endogenous PLCepsilon and the PLCbeta isoform, PLCbeta3, in Rat-1 fibroblasts. Examination of the temporal activation of these PLC isoforms, however, reveals agonist- and isoform-specific profiles. PLCbeta3 is activated acutely within the first minute of ET-1, LPA, or thrombin stimulation but does not contribute to sustained PI hydrolysis induced by LPA or thrombin and accounts for only part of ET-1 sustained stimulation. PLCepsilon, on the other hand, predominantly accounts for sustained PI hydrolysis. Consistent with this observation, reconstitution of PLCepsilon in knockdown cells dose-dependently increases sustained, but not acute, agonist-stimulated PI hydrolysis. Furthermore, combined knockdown of both PLCepsilon and PLCbeta3 additively inhibits PI hydrolysis, suggesting independent regulation of each isoform. Importantly, ubiquitination of inositol 1,4,5-trisphosphate receptors correlates with sustained, but not acute, activation of PLCepsilon or PLCbeta3. In conclusion, GPCR agonists ET-1, LPA, and thrombin activate endogenous PLCepsilon and PLCbeta3 in Rat-1 fibroblasts. Activation of these PLC isoforms displays agonist-specific temporal profiles; however, PLCbeta3 is predominantly involved in acute and PLCepsilon in sustained PI hydrolysis.
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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.