ArticleThe Journal of biological chemistry2020
Functional and structural characterization of allosteric activation of phospholipase Cε by Rap1A.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed, 11 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
- Cryo-EM structure of phospholipase Cε defines N-terminal domains and their roles in activity.Communications biology · 2025Article
- RhoA allosterically activates phospholipase Cε via its EF hands.Communications biology · 2025Article
- Small-angle X-ray scattering studies of enzymes.Current opinion in chemical biology · 2023Review
- Soluble cyclase-mediated nuclear cAMP synthesis is sufficient for cell proliferation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Structure and regulation of phospholipase Cβ and ε at the membrane.Chemistry and physics of lipids · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Phospholipase Cε (PLCε) is activated downstream of G protein-coupled receptors and receptor tyrosine kinases through direct interactions with small GTPases, including Rap1A and Ras. Although Ras has been reported to allosterically activate the lipase, it is not known whether Rap1A has the same ability or what its molecular mechanism might be. Rap1A activates PLCε in response to the stimulation of β-adrenergic receptors, translocating the complex to the perinuclear membrane. Because the C-terminal Ras association (RA2) domain of PLCε was proposed to the primary binding site for Rap1A, we first confirmed using purified proteins that the RA2 domain is indeed essential for activation by Rap1A. However, we also showed that the PLCε pleckstrin homology (PH) domain and first two EF hands (EF1/2) are required for Rap1A activation and identified hydrophobic residues on the surface of the RA2 domain that are also necessary. Small-angle X-ray scattering showed that Rap1A binding induces and stabilizes discrete conformational states in PLCε variants that can be activated by the GTPase. These data, together with the recent structure of a catalytically active fragment of PLCε, provide the first evidence that Rap1A, and by extension Ras, allosterically activate the lipase by promoting and stabilizing interactions between the RA2 domain and the PLCε core.
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What OpenQuestion holds
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.