ArticlePLoS biology2017
Proteolytic Origin of the Soluble Human IL-6R In Vivo and a Decisive Role of N-Glycosylation.
Article in PLoS biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 133 citations in OpenAlex.
- A randomized, double-blind, placebo-controlled trial of intravenous alpha-1 antitrypsin for ARDS secondary to COVID-19.Med (New York, N.Y.) · 2022Trial
- Refining therapeutic targeting of interleukin-6 by signalling mode selectivity.Nature reviews. Drug discovery · 2026Review
- Mesenchymal stromal cells immunosuppress osteoarthritis synovial fluid modulated monocytes via IL-6 and CCL2.Cell death & disease · 2026Article
- Article
- IL-6R blockade with tocilizumab disrupts pericyte- and tumor cell-driven IL-6/STAT3 signaling, enhancing docetaxel efficacy in ER+ breast cancer.bioRxiv : the preprint server for biology · 2026Article
- ADAM17 as a proteolytic rheostat linking inflammation, tissue repair, and failure of inflammatory resolution in liver injury and fibrosis.Frontiers in pharmacology · 2026Review
- Targeting asparagine and cysteine in SARS-CoV-2 variants and human pro-inflammatory mediators to alleviate COVID-19 severity; a cross-section and in-silico study.Scientific reports · 2025Article
- Molecular Epidemiology of Human Metapneumovirus Infections in Children from San Luis Potosí-Mexico.Viruses · 2025Article
- In-depth analysis of the tear fluid glycoproteome reveals diverse lacritin glycosylation and spliceoforms.The Journal of biological chemistry · 2025Article
- Association of the IL-6R rs2228145 polymorphism with diabetic nephropathy: A case-control study.Journal of diabetes investigation · 2025Article
- Intratumoral Delivery of Genetically Engineered Anti-IL-6 Trans-signaling Therapeutics.Molecular biotechnology · 2025Article
- In-depth analysis of the tear fluid glycoproteome reveals diverse lacritin glycosylation and spliceoforms.bioRxiv : the preprint server for biology · 2025Article
- The biology of interleukin-6 family cytokines is regulated by glycosylation.The Biochemical journal · 2025Review
- Controversies and insights into cytokine regulation of neurogenesis and behavior in adult rodents.Frontiers in immunology · 2025Review
- IL-6 Signaling in Immunopathology: From Basic Biology to Selective Therapeutic Intervention.ImmunoTargets and therapy · 2025Review
- RECK as a Potential Crucial Molecule for the Targeted Treatment of Sepsis.Journal of inflammation research · 2025Review
- Quantification and Site-Specific Analysis of Co-occupied N- and O-Glycopeptides.Journal of proteome research · 2024Article
- Genome-wide studies define new genetic mechanisms of IgA vasculitis.medRxiv : the preprint server for health sciences · 2024Article
- Quantification and site-specific analysis of co-occupied N- and O-glycopeptides.bioRxiv : the preprint server for biology · 2024Article
- Ectodomain shedding of PLA2R1 is mediated by the metalloproteases ADAM10 and ADAM17.The Journal of biological chemistry · 2024Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
24 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Signaling of the cytokine interleukin-6 (IL-6) via its soluble IL-6 receptor (sIL-6R) is responsible for the proinflammatory properties of IL-6 and constitutes an attractive therapeutic target, but how the sIL-6R is generated in vivo remains largely unclear. Here, we use liquid chromatography-mass spectrometry to identify an sIL-6R form in human serum that originates from proteolytic cleavage, map its cleavage site between Pro-355 and Val-356, and determine the occupancy of all O- and N-glycosylation sites of the human sIL-6R. The metalloprotease a disintegrin and metalloproteinase 17 (ADAM17) uses this cleavage site in vitro, and mutation of Val-356 is sufficient to completely abrogate IL-6R proteolysis. N- and O-glycosylation were dispensable for signaling of the IL-6R, but proteolysis was orchestrated by an N- and O-glycosylated sequon near the cleavage site and an N-glycan exosite in domain D1. Proteolysis of an IL-6R completely devoid of glycans is significantly impaired. Thus, glycosylation is an important regulator for sIL-6R generation.
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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.