Evidence map›Paper›PMID 26350460›Full record

ArticleThe Journal of biological chemistry2015

Thrombin promotes sustained signaling and inflammatory gene expression through the CDC25 and Ras-associating domains of phospholipase Cϵ.

Stephanie S Dusaban, Maya T Kunkel, Alan V Smrcka, Joan Heller Brown

Open access · hybridAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.8field-weighted citation impact, top 24% 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

14 citing papers in PubMed, 19 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Phospholipase Cε insufficiency causes ascending aortic aneurysm and dissection.American journal of physiology. Heart and circulatory physiology · 2022
    Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Phospholipase C-ε signaling mediates endothelial cell inflammation and barrier disruption in acute lung injury.American journal of physiology. Lung cellular and molecular physiology · 2016
    Article
  13. Article
  14. 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 2 institutions in 1 country.

Stephanie S DusabanFrom the Department of Pharmacology, School of Medicine and Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, California 92093 and.
Maya T KunkelFrom the Department of Pharmacology, School of Medicine and.
Alan V SmrckaDepartment of Pharmacology and Physiology, University of Rochester, Rochester, New York 14642.
Joan Heller BrownFrom the Department of Pharmacology, School of Medicine and jhbrown@ucsd.edu.
University of California, San Diego · USUniversity of Rochester · US

Funding

GRADUATE TRAINING IN CELLULAR &MOLECULAR PHARMACOLOGYT32GM007752 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BROWN, JOAN HELLER, HANDEL, TRACY M · 1985 to 2023
$13.5M
SIGNAL TRANSDUCTION BY G PROTEINR01GM053536 · NIGMS · UNIVERSITY OF ROCHESTER · PI SMRCKA, ALAN V. · 1996 to 2018
$4.9M
RhoA mediated survival signals in cardiomyocytesR37HL028143 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BROWN, JOAN HELLER · 2010 to 2019
$4.0M
THROMBIN, GALPHA12, AND RHO AND CELL GROWTHR01GM036927 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BROWN, JOAN HELLER · 1986 to 2012
$3.4M
RhoA and GPCR mediated transcriptional activation regulates glioblastomaR01CA218859 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BROWN, JOAN HELLER · 2018 to 2022
$2.3M
Coordination of signaling at the NHERF scaffoldR03CA178524 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KUNKEL, MAYA T · 2014 to 2015
$155k
NCI NIH HHS R01 CA218859NCI NIH HHS R03 CA178524NCI NIH HHS R03CA178524NHLBI NIH HHS R37 HL028143NIGMS NIH HHS R01 GM036927NIGMS NIH HHS R01 GM053536NIGMS NIH HHS R01GM36927NIGMS NIH HHS R01GM53536NIGMS NIH HHS T32 GM007752NIGMS NIH HHS T32GM007752
6 · The paper itself

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.

Indexed as

AnimalsAnimals, NewbornAstrocytesCell CompartmentationFluorescence Resonance Energy TransferGene Expression RegulationGolgi ApparatusInflammationInositol 1,4,5-TrisphosphateMiceMice, Inbred C57BLMice, TransgenicPhosphoinositide Phospholipase CPrimary Cell CultureProtein Kinase CProtein Structure, TertiaryInositol 1,4,5-TrisphosphatePhosphoinositide Phospholipase Cphospholipase C epsilonProtein Kinase Cprotein kinase Drap1 GTP-Binding Proteinsras-GRF1Thrombinastrocytecyclooxygenase (COX)diacylglycerolG protein-coupled receptor (GPCR)guanine nucleotide exchange factor (GEF)Phospholipase Cprotein kinase D (PKD)Ras-related protein 1 (Rap1)thrombin

Identifiers

PMID26350460
PMCPMC4646330
OpenAlexW2225183135

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.