Evidence map›Paper›PMID 27044325›Full record

ArticleBiology open2016

VEGF-A isoforms program differential VEGFR2 signal transduction, trafficking and proteolysis.

Gareth W Fearnley, Gina A Smith, Izma Abdul-Zani, Nadira Yuldasheva, Nadeem A Mughal, Shervanthi Homer-Vanniasinkam, Mark T Kearney, Ian C Zachary, Darren C Tomlinson, Michael A Harrison and 2 more

Open access · goldAbstract read
In one paragraph

Article in Biology open, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
4.0field-weighted citation impact, top 6% 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

43 citing papers in PubMed, 60 citations in OpenAlex.

  1. VEGFAngiogenesis · 2026
    Article
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  3. Quantification of vitreous VEGF-A121 and VEGF-A165 using an isoform-specific ELISA in proliferative diabetic retinopathy.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026
    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

12 authors at 3 institutions in 1 country.

Gareth W FearnleyEndothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK.
Gina A SmithEndothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK.
Izma Abdul-ZaniEndothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK.
Nadira YuldashevaLeeds Institute of Cardiovascular Metabolism and Medicine, LIGHT Laboratories, University of Leeds, Leeds LS2 9JT, UK.
Nadeem A MughalEndothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK.
Shervanthi Homer-VanniasinkamLeeds Vascular Institute, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK.
Mark T KearneyLeeds Institute of Cardiovascular Metabolism and Medicine, LIGHT Laboratories, University of Leeds, Leeds LS2 9JT, UK.
Ian C ZacharyCentre for Cardiovascular Biology and Medicine, Division of Medicine, University College London, London WC1E 6BT, UK.
Darren C TomlinsonBiomedical Health Research Centre, Astbury Building, University of Leeds, Leeds LS2 9JT, UK.
Michael A HarrisonSchool of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UK.
Stephen B WheatcroftLeeds Institute of Cardiovascular Metabolism and Medicine, LIGHT Laboratories, University of Leeds, Leeds LS2 9JT, UK.
Sreenivasan PonnambalamEndothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK s.ponnambalam@leeds.ac.uk.
University of Leeds · GBLeeds General Infirmary · GBUniversity College London · GB

Funding

British Heart Foundation FS/12/20/29462British Heart Foundation FS/12/71/29747British Heart Foundation PG/12/56/29748British Heart Foundation PG/14/54/30939British Heart Foundation RG/06/003/21131British Heart Foundation RG/09/010/28087British Heart Foundation RG/11/11/29050British Heart Foundation RG/15/7/31521Medical Research Council MR/L009625/1
6 · The paper itself

Abstract

Vascular endothelial growth factor A (VEGF-A) binding to the receptor tyrosine kinase VEGFR2 triggers multiple signal transduction pathways, which regulate endothelial cell responses that control vascular development. Multiple isoforms of VEGF-A can elicit differential signal transduction and endothelial responses. However, it is unclear how such cellular responses are controlled by isoform-specific VEGF-A-VEGFR2 complexes. Increasingly, there is the realization that the membrane trafficking of receptor-ligand complexes influences signal transduction and protein turnover. By building on these concepts, our study shows for the first time that three different VEGF-A isoforms (VEGF-A165, VEGF-A121 and VEGF-A145) promote distinct patterns of VEGFR2 endocytosis for delivery into early endosomes. This differential VEGFR2 endocytosis and trafficking is linked to VEGF-A isoform-specific signal transduction events. Disruption of clathrin-dependent endocytosis blocked VEGF-A isoform-specific VEGFR2 activation, signal transduction and caused substantial depletion in membrane-bound VEGFR1 and VEGFR2 levels. Furthermore, such VEGF-A isoforms promoted differential patterns of VEGFR2 ubiquitylation, proteolysis and terminal degradation. Our study now provides novel insights into how different VEGF-A isoforms can bind the same receptor tyrosine kinase and elicit diverse cellular outcomes.

Indexed as

EndothelialTraffickingVEGF-AVEGFR2

Identifiers

PMID27044325
PMCPMC4874356
OpenAlexW2311113928

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.