ArticlePloS one2014
N-terminal cleavage and release of the ectodomain of Flt1 is mediated via ADAM10 and ADAM 17 and regulated by VEGFR2 and the Flt1 intracellular domain.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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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.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Temporal inhibition of ADAM17 in fibroblasts reduces stiffness and promotes vascularization following myocardial infarction.Cardiovascular research · 2026Article
- Exploring the mechanism of plasticizers action in liver damage based on network toxicology, molecular docking, and molecular dynamic simulation.Scientific reports · 2025Article
- Human liver single nuclear RNA sequencing implicates BMPR2, GDF15, arginine, and estrogen in portopulmonary hypertension.Communications biology · 2023Article
- Placental Transcription Profiling in 6-23 Weeks' Gestation Reveals Differential Transcript Usage in Early Development.International journal of molecular sciences · 2022Article
- Regulation of Platelet-Derived ADAM17: A Biomarker Approach for Breast Cancer?Diagnostics (Basel, Switzerland) · 2021Article
- Contribution of ADAM17 and related ADAMs in cardiovascular diseases.Cellular and molecular life sciences : CMLS · 2021Review
- Proteolytic Cleavage of Receptor Tyrosine Kinases.Biomolecules · 2021Review
- Review
- VEGF-A selectively inhibits FLT1 ectodomain shedding independent of receptor activation and receptor endocytosis.American journal of physiology. Cell physiology · 2018Article
- Transactivated Epidermal Growth Factor Receptor Recruitment of α-actinin-4 From F-actin Contributes to Invasion of Brain Microvascular Endothelial Cells by MeningiticFrontiers in cellular and infection microbiology · 2018Article
- Recent Advances in ADAM17 Research: A Promising Target for Cancer and Inflammation.Mediators of inflammation · 2017Review
- Hydrogen Sulfide Inhibits High Glucose-Induced sFlt-1 Production via Decreasing ADAM17 Expression in 3T3-L1 Adipocytes.International journal of endocrinology · 2017Article
- Ectodomain cleavage of FLT1 regulates receptor activation and function and is not required for its downstream intracellular cleavage.Experimental cell research · 2016Article
- Proteolytic cleavage, trafficking, and functions of nuclear receptor tyrosine kinases.The FEBS journal · 2015Review
- Aspirin inhibits expression of sFLT1 from human cytotrophoblasts induced by hypoxia, via cyclo-oxygenase 1.Placenta · 2015Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Flt is one of the cell surface VEGF receptors which can be cleaved to release an N-terminal extracellular fragment which, like alternately transcribed soluble Flt1 (sFlt1), can antagonize the effects of VEGF. In HUVEC and in HEK293 cells where Flt1 was expressed, metalloprotease inhibitors reduced Flt1 N-terminal cleavage. Overexpression of ADAM10 and ADAM17 increased cleavage while knockdown of ADAM10 and ADAM17 reduced N-terminal cleavage suggesting that these metalloproteases were responsible for Flt1 cleavage. Protein kinase C (PKC) activation increased the abundance and the cleavage of Flt1 but this did not require any residues within the intracellular portion of Flt1. ALLN, a proteasomal inhibitor, increased the abundance of Flt1 which was additive to the effect of PKC. Removal of the entire cytosolic region of Flt1 appeared to stimulate cleavage of Flt1 and Flt1 was no longer sensitive to ALLN suggesting that the cytosolic region contained a degradation domain. Knock down of c-CBL, a ring finger ubiquitin ligase, in HEK293 cells increased the expression of Flt1 although it did not appear to require a previously published tyrosine residue (1333Y) in the C-terminus of Flt1. Increasing VEGFR2 expression increased VEGF-stimulated sFlt1 expression and progressively reduced the cleavage of Flt1 with Flt1 staying bound to VEGFR2 as a heterodimer. Our results imply that secreted sFlt1 and cleaved Flt1 will tend to have local effects as a VEGF antagonist when released from cells expressing VEGFR2 and more distant effects when released from cells lacking VEGFR2.
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Registered trials
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.