Evidence map›Paper›PMID 25193662›Full record

ArticleThe Journal of biological chemistry2014

Membrane-induced allosteric control of phospholipase C-β isozymes.

Thomas H Charpentier, Gary L Waldo, Matthew O Barrett, Weigang Huang, Qisheng Zhang, T Kendall Harden, John Sondek

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.7field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 39 citations in OpenAlex.

  1. Article
  2. Anionic lipids regulate PLCbioRxiv : the preprint server for biology · 2026
    Article
  3. Article
  4. An integrated mechanism of GProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  5. A molecular mechanism to diversify CaNature communications · 2024
    Article
  6. The mechanism ofProceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  7. Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Activation of Phospholipase C β by Gβγ and GαStructure (London, England : 1993) · 2020
    Article
  13. Article
  14. Article
  15. Article
  16. The binding of activated GαThe Journal of biological chemistry · 2017
    Article
  17. Article
  18. Phospholipase Cβ1 induces membrane tubulation and is involved in caveolae formation.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Thomas H CharpentierFrom the Departments of Pharmacology and.
Gary L WaldoFrom the Departments of Pharmacology and.
Matthew O BarrettFrom the Departments of Pharmacology and.
Weigang Huangthe Division of Chemical Biology and Medicinal Chemistry, University of North Carolina School of Pharmacy, Chapel Hill, North Carolina 27599.
Qisheng Zhangthe Division of Chemical Biology and Medicinal Chemistry, University of North Carolina School of Pharmacy, Chapel Hill, North Carolina 27599.
T Kendall HardenFrom the Departments of Pharmacology and.
John SondekFrom the Departments of Pharmacology and Biochemistry and Biophysics and the Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599 and sondek@med.unc.edu.
University of North Carolina at Chapel Hill · USUNC Lineberger Comprehensive Cancer Center

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI David Darr · 1985 to 2026
$201.5M
Regulation of Phospholipase CR01GM057391 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SONDEK, JOHN E · 1998 to 2021
$6.9M
High-throughput screens to identify modulators of phospholipase C isozymesR01GM098894 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SONDEK, JOHN E, ZHANG, QISHENG · 2011 to 2013
$834k
NCI NIH HHS P30 CA016086NIGMS NIH HHS R01-GM0557391NIGMS NIH HHS R01 GM057391NIGMS NIH HHS R01 GM098894NIGMS NIH HHS R01-GM098894
6 · The paper itself

Abstract

All peripheral membrane proteins must negotiate unique constraints intrinsic to the biological interface of lipid bilayers and the cytosol. Phospholipase C-β (PLC-β) isozymes hydrolyze the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) to propagate diverse intracellular responses that underlie the physiological action of many hormones, neurotransmitters, and growth factors. PLC-β isozymes are autoinhibited, and several proteins, including Gαq, Gβγ, and Rac1, directly engage distinct regions of these phospholipases to release autoinhibition. To understand this process, we used a novel, soluble analog of PIP2 that increases in fluorescence upon cleavage to monitor phospholipase activity in real time in the absence of membranes or detergents. High concentrations of Gαq or Gβ1γ2 did not activate purified PLC-β3 under these conditions despite their robust capacity to activate PLC-β3 at membranes. In addition, mutants of PLC-β3 with crippled autoinhibition dramatically accelerated the hydrolysis of PIP2 in membranes without an equivalent acceleration in the hydrolysis of the soluble analog. Our results illustrate that membranes are integral for the activation of PLC-β isozymes by diverse modulators, and we propose a model describing membrane-mediated allosterism within PLC-β isozymes.

Indexed as

Allosteric RegulationAnimalsBiocatalysisCell MembraneChlorocebus aethiopsCOS CellsFluorescent DyesGenes, ReporterHeterotrimeric GTP-Binding ProteinsHumansHydrolysisIsoenzymesModels, BiologicalPhosphatidylinositol 4,5-DiphosphatePhospholipase C betaProtein Structure, SecondaryFluorescent DyesHeterotrimeric GTP-Binding ProteinsIsoenzymesPhosphatidylinositol 4,5-DiphosphatePhospholipase C betaPLCB3 protein, humanFluorescenceG ProteinMembranePhospholipase CPhospholipid

Identifiers

PMID25193662
PMCPMC4207972
OpenAlexW1987427597

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.