Evidence map›Paper›PMID 25733681›Full record

ArticleMolecular and cellular biology2015

RasGAP Promotes Autophagy and Thereby Suppresses Platelet-Derived Growth Factor Receptor-Mediated Signaling Events, Cellular Responses, and Pathology.

Hetian Lei, Cynthia X Qian, Jinghu Lei, Luis J Haddock, Shizuo Mukai, Andrius Kazlauskas

Open access · bronzeAbstract read
In one paragraph

Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

19 citing papers in PubMed, 30 citations in OpenAlex.

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  11. AAV-CRISPR/Cas9-Mediated Depletion of VEGFR2 Blocks Angiogenesis In Vitro.Investigative ophthalmology & visual science · 2017
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  16. Editing VEGFR2 Blocks VEGF-Induced Activation of Akt and Tube Formation.Investigative ophthalmology & visual science · 2017
    Article
  17. 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

6 authors at 2 institutions in 1 country.

Hetian LeiSchepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA.
Cynthia X QianMassachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA.
Jinghu LeiBoston Latin School, Boston, Massachusetts, USA.
Luis J HaddockMassachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA.
Shizuo MukaiMassachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA.
Andrius KazlauskasSchepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA Andrius_kazlauskas@meei.harvard.edu.
Massachusetts Eye and Ear Infirmary · USBoston Latin Academy · US

Funding

PDGF and PVRR01EY012509 · NEI · SCHEPENS EYE RESEARCH INSTITUTE · PI LEI, HETIAN · 2000 to 2017
$8.5M
NEI NIH HHS EY012509NEI NIH HHS R01 EY012509
6 · The paper itself

Abstract

Platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) make profound contributions to both physiology and pathology. While it is widely believed that direct (PDGF-mediated) activation is the primary mode of activating PDGFRs, the discovery that they can also be activated indirectly begs the question of the relevance of the indirect mode of activating PDGFRs. In the context of a blinding eye disease, indirect activation of PDGFRα results in persistent signaling, which suppresses the level of p53 and thereby promotes viability of cells that drive pathogenesis. Under the same conditions, PDGFRβ fails to undergo indirect activation. In this paper, we report that RasGAP (GTPase-activating protein of Ras) prevented indirect activation of PDGFRβ. RasGAP, which associates with PDGFRβ but not PDGFRα, reduced the level of mitochondrion-derived reactive oxygen species, which are required for enduring activation of PDGFRs. Furthermore, preventing PDGFRβ from associating with RasGAP allowed it to signal enduringly and drive pathogenesis of a blinding eye disease. These results indicate a previously unappreciated role of RasGAP in antagonizing indirect activation of PDGFRβ, define the underlying mechanism, and raise the possibility that PDGFRβ-mediated diseases involve indirect activation of PDGFRβ.

Indexed as

AnimalsAutophagyGene Expression RegulationHEK293 CellsHumansMicep120 GTPase Activating ProteinReactive Oxygen SpeciesReceptor, Platelet-Derived Growth Factor alphaReceptor, Platelet-Derived Growth Factor betaSignal Transductionp120 GTPase Activating ProteinReactive Oxygen SpeciesReceptor, Platelet-Derived Growth Factor alphaReceptor, Platelet-Derived Growth Factor beta

Identifiers

PMID25733681
PMCPMC4405646
OpenAlexW2139168590

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.