ArticleProceedings of the National Academy of Sciences of the United States of America2015
A systematic study of modulation of ADAM-mediated ectodomain shedding by site-specific O-glycosylation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 119 citations in OpenAlex.
- Site-specific O-glycans influence lacritin structure and multimerization in tears.Protein science : a publication of the Protein Society · 2026Article
- Protein O-Glycosylation Shapes Lymphatic Endothelia and Lymph Node Macrophage Populations.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Murine ADAM15 Deficiency Is Associated With Atrial Remodelling and Atrial Arrhythmia Susceptibility.European journal of clinical investigation · 2026Article
- Integrated Network and Transcriptomic Analyses Identify a Candidate Ethanol-ADAM17 Molecular Axis Associated with Glioblastoma Progression.International journal of molecular sciences · 2026Article
- Article
- ST8Sia6-dependent glycosylation restrains gut inflammation and pathogenic TCell reports · 2026Article
- The ADAM Family of Proteases: Structure, Substrates, and Roles in Liver Diseases.International journal of molecular sciences · 2026Review
- Beyond Structure: The Dynamic Role of the Extracellular Matrix Components in Immune Evasion.Cancer communications (London, England) · 2026Review
- In-depth analysis of the tear fluid glycoproteome reveals diverse lacritin glycosylation and spliceoforms.The Journal of biological chemistry · 2025Article
- In-depth analysis of the tear fluid glycoproteome reveals diverse lacritin glycosylation and spliceoforms.bioRxiv : the preprint server for biology · 2025Article
- Engineered Proteins and Chemical Tools to Probe the Cell Surface Proteome.Chemical reviews · 2025Review
- Altered O-glycosylation of βThe FEBS journal · 2025Article
- Implications of glycosylation for the development of selected cytokines and their derivatives for medical use.Biotechnology advances · 2024Review
- Genome-wide studies define new genetic mechanisms of IgA vasculitis.medRxiv : the preprint server for health sciences · 2024Article
- Substrate O-glycosylation actively regulates extracellular proteolysis.Protein science : a publication of the Protein Society · 2024Article
- Sequential glycosylations at the multibasic cleavage site of SARS-CoV-2 spike protein regulate viral activity.Nature communications · 2024Article
- RNA-Sequencing Characterization of lncRNA and mRNA Functions in Septic Pig Liver Injury.Genes · 2023Article
- Comprehensive analysis of platelet glycoprotein Ibα ectodomain glycosylation.Journal of thrombosis and haemostasis : JTH · 2023Article
- Presenilin 1 deficiency impairs Aβ42-to-Aβ40- and angiotensin-converting activities of ACE.Frontiers in aging neuroscience · 2023Article
- O-glycosylation and its role in therapeutic proteins.Bioscience reports · 2022Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Regulated shedding of the ectodomain of cell membrane proteins by proteases is a common process that releases the extracellular domain from the cell and activates cell signaling. Ectodomain shedding occurs in the immediate extracellular juxtamembrane region, which is also where O-glycosylation is often found and examples of crosstalk between shedding and O-glycosylation have been reported. Here, we systematically investigated the potential of site-specific O-glycosylation mediated by distinct polypeptide GalNAc-transferase (GalNAc-T) isoforms to coregulate ectodomain shedding mediated by the A Disintegrin And Metalloproteinase (ADAM) subfamily of proteases and in particular ADAM17. We analyzed 25 membrane proteins that are known to undergo ADAM17 shedding and where the processing sites included Ser/Thr residues within ± 4 residues that could represent O-glycosites. We used in vitro GalNAc-T enzyme and ADAM cleavage assays to demonstrate that shedding of at least 12 of these proteins are potentially coregulated by O-glycosylation. Using TNF-α as an example, we confirmed that shedding mediated by ADAM17 is coregulated by O-glycosylation controlled by the GalNAc-T2 isoform both ex vivo in isogenic cell models and in vivo in mouse Galnt2 knockouts. The study provides compelling evidence for a wider role of site-specific O-glycosylation in ectodomain shedding.
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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.