Evidence map›Paper›PMID 25435326›Full record

ArticleStructure (London, England : 1993)2014

Molecular mechanisms of phospholipase C β3 autoinhibition.

Angeline M Lyon, Jessica A Begley, Taylor D Manett, John J G Tesmer

Open access · greenAbstract read
In one paragraph

Article in Structure (London, England : 1993), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
0.9field-weighted citation impact, top 28% 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

26 citing papers in PubMed, 46 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. A molecular mechanism to diversify CaNature communications · 2024
    Article
  5. 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. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. GαBiochemistry · 2019
    Article
  17. Article
  18. 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

4 authors at 1 institution in 1 country.

Angeline M LyonLife Sciences Institute, University of Michigan, 210 Washtenaw Avenue, Ann Arbor, MI 48109-2216, USA; Department of Pharmacology, University of Michigan, 1150 W. Medical Center Drive, 1301 MSRB III, Ann Arbor, MI 48109, USA; Department of Biological Chemistry, University of Michigan, 1150 W. Medical Center Drive, RM 5301 MSRB III, Ann Arbor, MI 48109-0600, USA.
Jessica A BegleyLife Sciences Institute, University of Michigan, 210 Washtenaw Avenue, Ann Arbor, MI 48109-2216, USA; Department of Pharmacology, University of Michigan, 1150 W. Medical Center Drive, 1301 MSRB III, Ann Arbor, MI 48109, USA; Department of Biological Chemistry, University of Michigan, 1150 W. Medical Center Drive, RM 5301 MSRB III, Ann Arbor, MI 48109-0600, USA.
Taylor D ManettLife Sciences Institute, University of Michigan, 210 Washtenaw Avenue, Ann Arbor, MI 48109-2216, USA; Department of Pharmacology, University of Michigan, 1150 W. Medical Center Drive, 1301 MSRB III, Ann Arbor, MI 48109, USA; Department of Biological Chemistry, University of Michigan, 1150 W. Medical Center Drive, RM 5301 MSRB III, Ann Arbor, MI 48109-0600, USA.
John J G TesmerLife Sciences Institute, University of Michigan, 210 Washtenaw Avenue, Ann Arbor, MI 48109-2216, USA; Department of Pharmacology, University of Michigan, 1150 W. Medical Center Drive, 1301 MSRB III, Ann Arbor, MI 48109, USA; Department of Biological Chemistry, University of Michigan, 1150 W. Medical Center Drive, RM 5301 MSRB III, Ann Arbor, MI 48109-0600, USA. Electronic address: tesmerjj@umich.edu.
Washtenaw Community College · US

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Alexey I Nesvizhskii · 1988 to 2026
$178.2M
PUBLIC HEALTH DEMONSTRATIONP60DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MYERS, MARTIN G · 1985 to 2012
$26.5M
Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3M
Structure, function, and inhibition of G protein-coupled receptor kinasesR01HL071818 · NHLBI · UNIVERSITY OF TEXAS AUSTIN · PI TESMER, JOHN · 2004 to 2023
$7.1M
Structural Studies of Galphaq and Its Complexes at the Cell MembraneR01HL086865 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI TESMER, JOHN · 2007 to 2015
$3.0M
NCI NIH HHS P30 CA046592NCI NIH HHS P30 CA-46592NHLBI NIH HHS HL071818NHLBI NIH HHS HL086865NHLBI NIH HHS R01 HL071818NHLBI NIH HHS R01 HL086865NIDDK NIH HHS DK20572NIDDK NIH HHS P30 DK020572NIDDK NIH HHS P60 DK020572
6 · The paper itself

Abstract

Phospholipase C β (PLCβ) enzymes are dramatically activated by heterotrimeric G proteins. Central to this response is the robust autoinhibition of PLCβ by the X-Y linker region within its catalytic core and by the Hα2' helix in the C-terminal extension of the enzyme. The molecular mechanism of each and their mutual dependence are poorly understood. Herein, it is shown that distinct regions within the X-Y linker have specific roles in regulating activity. Most important,an acidic stretch within the linker stabilizes a lid that occludes the active site, consistent with crystal structures of variants lacking this region. Inhibition by the Hα2' helix is independent of the X-Y linker and likely regulates activity by limiting membrane interaction of the catalytic core. Full activation of PLCβ thus requires multiple independent molecular events induced by membrane association of the catalytic core and by the binding of regulatory proteins.

Indexed as

Models, MolecularCrystallography, X-RayHumansPhospholipase C betaProtein BindingProtein ConformationPhospholipase C beta

Identifiers

PMID25435326
PMCPMC4308481
OpenAlexW1965506881

What OpenQuestion holds

Textmetadata
LicenceTDM
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.