Evidence map›Paper›PMID 23911939›Full record

ArticleExperimental cell research2013

Protein kinase C regulates FLT1 abundance and stimulates its cleavage in vascular endothelial cells with the release of a soluble PlGF/VEGF antagonist.

Nandita S Raikwar, Kang Z Liu, Christie P Thomas

Open access · greenAbstract read
In one paragraph

Article in Experimental cell research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.5field-weighted citation impact, top 19% 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

18 citing papers in PubMed, 30 citations in OpenAlex.

  1. Trial
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  7. VEGFR1 signaling in retinal angiogenesis and microinflammation.Progress in retinal and eye research · 2021
    Review
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  9. Article
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  11. Molecular Pathways: Receptor Ectodomain Shedding in Treatment, Resistance, and Monitoring of Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017
    Review
  12. Article
  13. Review
  14. Article
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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

3 authors at 2 institutions in 1 country.

Nandita S RaikwarDepartment of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA, USA.
Kang Z Liu
Christie P Thomas
University of Iowa · USVeterans Health Administration · US

Funding

Expression of sFlt1 and its function in the glomerular endotheliumR01DK090053 · NIDDK · UNIVERSITY OF IOWA · PI THOMAS, CHRISTIE P. · 2010 to 2014
$1.6M
NIDDK NIH HHS R01 DK090053NIDDK NIH HHS R01DK090053
6 · The paper itself

Abstract

FLT1 and its soluble form (sFLT1) arise as alternate transcripts from the same gene and sFLT1 can antagonize the effect of vascular endothelial growth factor (VEGF) on its cognate receptors. We investigated the effect of VEGF and protein kinase C (PKC) activation on sFLT1 abundance. We demonstrated that VEGF stimulates sFLT1 and FLT1 mRNA and protein levels in vascular endothelial cells via VEGFR2 and PKC. Using an FLT1 expression vector with N and C-terminal epitope tags, we show that PKC activation increases the cleavage of FLT1 into an N-terminal extracellular fragment and a C-terminal intracellular fragment with the cleavage occurring adjacent to the transmembrane domain. The trafficking and glycosylation inhibitors brefeldin, monensin and tunicamycin substantially reduced cleavage and release of the N-terminal ectodomain of FLT1 and inhibited secretion of the isoforms of sFLT1. The shed FLT1 ectodomain can bind VEGF and PlGF and inhibit VEGF-induced vascular tube formation thus confirming that it is functionally equivalent to the alternately spliced and secreted sFLT1 isoforms.

Indexed as

ProteolysisAnimalsChlorocebus aethiopsCOS CellsHEK293 CellsHumansHuman Umbilical Vein Endothelial CellsMembrane ProteinsProtein IsoformsProtein Kinase CProtein Structure, TertiaryTranscription, GeneticVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1Vascular Endothelial Growth Factor Receptor-2FLT1 protein, humanMembrane ProteinsPIGF protein, humanProtein IsoformsProtein Kinase CVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1Vascular Endothelial Growth Factor Receptor-2VEGFA protein, humanAngiogenesisProteolytic cleavageSoluble receptor

Identifiers

PMID23911939
PMCPMC3797157
OpenAlexW1998067618

What OpenQuestion holds

Textmetadata
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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.