ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2021
Interleukin-11 (IL-11) receptor cleavage by the rhomboid protease RHBDL2 induces IL-11 trans-signaling.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- Interleukin-11 Signaling in Liver Disease: Mechanisms, Cellular Crosstalk, and Therapeutic Potential.Biomolecules · 2026Review
- Rhomboid protease RHBDL2 is a calcium-activated suppressor of EGFR signalling in keratinocytes.Cellular and molecular life sciences : CMLS · 2026Article
- Triple-Negative Breast Cancer Cells Resist Natural Killer Cell-Mediated Killing Through Interleukin-11 Trans-Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Holding Out for a Model: Rhomboid Superfamily in Vertebrate Development and Disease.Journal of cellular physiology · 2025Review
- The biology of interleukin-6 family cytokines is regulated by glycosylation.The Biochemical journal · 2025Review
- IL-6 Signaling in Immunopathology: From Basic Biology to Selective Therapeutic Intervention.ImmunoTargets and therapy · 2025Review
- Review
- Long-term increase in soluble interleukin-6 receptor levels in convalescents after mild COVID-19 infection.Frontiers in immunology · 2024Article
- The role of interleukin-6 classic and trans-signaling and interleukin-11 classic signaling in gastric cancer cells.Contemporary oncology (Poznan, Poland) · 2024Article
- Targeting IL-6 trans-signalling: past, present and future prospects.Nature reviews. Immunology · 2023Review
- The interleukin-11 receptor variant p.W307R results in craniosynostosis in humans.Scientific reports · 2023Article
- Coding variants of the interleukin-11 receptor with reduced protein maturation show protease-dependent trans-signaling and transduce normal STAT3 signaling.Genes & diseases · 2023Article
- Soluble CD25 imposes a low-zone IL-2 signaling environment that favors competitive outgrowth of antigen-experienced CD25Cellular immunology · 2023Article
- RHBDL2 promotes the proliferation, migration, and invasion of pancreatic cancer by stabilizing the N1ICD via the OTUD7B and activating the Notch signaling pathway.Cell death & disease · 2022Article
- The collectrin-like part of the SARS-CoV-1 and -2 receptor ACE2 is shed by the metalloproteinases ADAM10 and ADAM17.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Soluble forms of cytokine and growth factor receptors: mechanisms of generation and modes of action in the regulation of local and systemic inflammation.FEBS letters · 2022Review
- The Role of Interleukin-6 Family Members in Cardiovascular Diseases.Frontiers in cardiovascular medicine · 2022Review
- Conformational surveillance of Orai1 by a rhomboid intramembrane protease prevents inappropriate CRAC channel activation.Molecular cell · 2021Article
- A single aromatic residue in sgp130Fc/olamkicept allows the discrimination between interleukin-6 and interleukin-11 trans-signaling.iScience · 2021Article
- Interleukin-11 (IL-11) receptor cleavage by the rhomboid protease RHBDL2 induces IL-11 trans-signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interleukin-11 (IL-11) is a pleiotropic cytokine with both pro- and anti-inflammatory properties. It activates its target cells via binding to the membrane-bound IL-11 receptor (IL-11R), which then recruits a homodimer of the ubiquitously expressed, signal-transducing receptor gp130. Besides this classic signaling pathway, IL-11 can also bind to soluble forms of the IL-11R (sIL-11R), and IL-11/sIL-11R complexes activate cells via the induction of gp130 homodimerization (trans-signaling). We have previously reported that the metalloprotease ADAM10 cleaves the membrane-bound IL-11R and thereby generates sIL-11R. In this study, we identify the rhomboid intramembrane protease RHBDL2 as a so far unrecognized alternative sheddase that can efficiently trigger IL-11R secretion. We determine the cleavage site used by RHBDL2, which is located in the extracellular part of the receptor in close proximity to the plasma membrane, between Ala-370 and Ser-371. Furthermore, we identify critical amino acid residues within the transmembrane helix that are required for IL-11R proteolysis. We also show that ectopically expressed RHBDL2 is able to cleave the IL-11R within the early secretory pathway and not only at the plasma membrane, indicating that its subcellular localization plays a central role in controlling its activity. Moreover, RHBDL2-derived sIL-11R is biologically active and able to perform IL-11 trans-signaling. Finally, we show that the human mutation IL-11R-A370V does not impede IL-11 classic signaling, but prevents RHBDL2-mediated IL-11R cleavage.
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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.