ArticleNature communications2016
Phosphatidylserine exposure is required for ADAM17 sheddase function.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
109 citing papers in PubMed, 1 synthesis or guideline pooled it, 164 citations in OpenAlex.
- Exercise interventions and serum IGF-1 levels in older adults with frailty and/or sarcopenia: a systematic review and meta analysis.Frontiers in public health · 2025Pooled it
- Beneficial vascular effects of oral phosphatidylserine supplementation in type 2 diabetes.Journal of applied physiology (Bethesda, Md. : 1985) · 2026Trial
- Lipid flip-flop in biological membranes: through the lens of TMEM16F.Physiological reviews · 2027Review
- Cell surface remodeling caused by the loss of the flippase subunit TMEM30A in immune cells.Journal of cell science · 2026Article
- Cell-autonomous control of CAR signaling and receptor shedding via ADAM17-mediated proteolysis.Cell · 2026Article
- Lipid-Facilitated Opening of the ADAM10 Sheddase Revealed by Enhanced Sampling Simulations.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- ADAM17-induced shedding of glypican-1 as a mechanism of impaired endothelial shear stress mechanotransduction.American journal of physiology. Cell physiology · 2026Article
- Mechanoresponsive ion channels Piezo1 and TRPV4 stimulate ADAM10 and ADAM17 with differential impact on endothelial migration and proliferation.Cell communication and signaling : CCS · 2026Article
- ADAM17 as a proteolytic rheostat linking inflammation, tissue repair, and failure of inflammatory resolution in liver injury and fibrosis.Frontiers in pharmacology · 2026Review
- Review
- ADAM17 as a promising therapeutic target: from structural basis to inhibitor discovery in human diseases.Frontiers in pharmacology · 2025Review
- Functional Interdependence of Anoctamins May Influence Conclusions from Overexpression Studies.International journal of molecular sciences · 2024Article
- Overcoming the Tumor Collagen Barriers: A Multistage Drug Delivery Strategy for DDR1-Mediated Resistant Colorectal Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Extracellular Vesicles as Mediators in Atherosclerotic Cardiovascular Disease.Journal of lipid and atherosclerosis · 2024Review
- TMEM16F scramblase regulates angiogenesis via endothelial intracellular signaling.Journal of cell science · 2024Article
- Targeting a disintegrin and metalloprotease (ADAM) 17-CD122 axis enhances CD8Signal transduction and targeted therapy · 2024Article
- Cryo-EM reveals that iRhom2 restrains ADAM17 protease activity to control the release of growth factor and inflammatory signals.Molecular cell · 2024Article
- SARS-CoV-2, periodontal pathogens, and host factors: The trinity of oral post-acute sequelae of COVID-19.Reviews in medical virology · 2024Review
- Whole blood coagulation in an ex vivo thrombus is sufficient to induce clot neutrophils to adopt a myeloid-derived suppressor cell signature and shed soluble Lox-1.Journal of thrombosis and haemostasis : JTH · 2024Article
- Niclosamide, but not ivermectin, inhibits anoctamin 1 and 6 and attenuates inflammation of the respiratory tract.Pflugers Archiv : European journal of physiology · 2024Article
49 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ADAM17, a prominent member of the 'Disintegrin and Metalloproteinase' (ADAM) family, controls vital cellular functions through cleavage of transmembrane substrates. Here we present evidence that surface exposure of phosphatidylserine (PS) is pivotal for ADAM17 to exert sheddase activity. PS exposure is tightly coupled to substrate shedding provoked by diverse ADAM17 activators. PS dependency is demonstrated in the following: (a) in Raji cells undergoing apoptosis; (b) in mutant PSA-3 cells with manipulatable PS content; and (c) in Scott syndrome lymphocytes genetically defunct in their capacity to externalize PS in response to intracellular Ca(2+) elevation. Soluble phosphorylserine but not phosphorylcholine inhibits substrate cleavage. The isolated membrane proximal domain (MPD) of ADAM17 binds to PS but not to phosphatidylcholine liposomes. A cationic PS-binding motif is identified in this domain, replacement of which abrogates liposome-binding and renders the protease incapable of cleaving its substrates in cells. We speculate that surface-exposed PS directs the protease to its targets where it then executes its shedding function.
Indexed as
Identifiers
What OpenQuestion holds
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.