ArticleThe Journal of biological chemistry2018
The AB loop of oncostatin M (OSM) determines species-specific signaling in humans and mice.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Patterns of Immune Activation in HIV and Non HIV Subjects and Its Relation to Cardiovascular Disease Risk.Frontiers in immunology · 2021Trial
- Oncostatin-M ligand-based CAR-T therapy displays robust anti-tumor activity against osteosarcoma.BMC medicine · 2026Article
- Neutrophil-derived oncostatin m contributes to endothelial cell dysfunction during Treponema denticola interaction.PloS one · 2026Article
- Development of the First Small-Molecule Inhibitor Targeting Oncostatin M for Treatment of Breast Cancer.Journal of medicinal chemistry · 2025Article
- Structures of complete extracellular assemblies of type I and type II Oncostatin M receptor complexes.Nature communications · 2024Article
- Oncostatin M receptor-dependent signaling assessed by RNA sequencing in mouse hematopoietic stem cells.Scientific data · 2024Article
- Characterization of anbioRxiv : the preprint server for biology · 2023Article
- Uncovering the promiscuous activity of IL-6 proteins: A multi-dimensional analysis of phylogeny, classification and residue conservation.Protein science : a publication of the Protein Society · 2022Article
- Stimulation of Osteoclast Formation by Oncostatin M and the Role of WNT16 as a Negative Feedback Regulator.International journal of molecular sciences · 2022Review
- The Role of Oncostatin M and Its Receptor Complexes in Cardiomyocyte Protection, Regeneration, and Failure.International journal of molecular sciences · 2022Review
- Concomitant Activation of OSM and LIF Receptor by a Dual-Specific hlOSM Variant Confers Cardioprotection after Myocardial Infarction in Mice.International journal of molecular sciences · 2021Article
- Oncostatin M Receptor-Targeted Antibodies Suppress STAT3 Signaling and Inhibit Ovarian Cancer Growth.Cancer research · 2021Article
- Article
- Ski mediates TGF-β1-induced fibrosarcoma cell proliferation and promotes tumor growth.Journal of Cancer · 2020Article
- Molecular Simulation of Oncostatin M and Receptor (OSM-OSMR) Interaction as a Potential Therapeutic Target for Inflammatory Bowel Disease.Frontiers in molecular biosciences · 2020Article
- Oncostatin M, an Underestimated Player in the Central Nervous System.Frontiers in immunology · 2019Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The pleiotropic interleukin-6 (IL-6)-type cytokine oncostatin M (OSM) signals in multiple cell types, affecting processes such as cell differentiation, hematopoiesis, and inflammation. In humans, OSM exerts its effects through activation of either of two different heterodimeric receptor complexes, formed by glycoprotein 130 (gp130) and either OSM receptor (OSMR) or leukemia inhibitory factor receptor (LIFR). In contrast, the mouse OSM orthologue acts mainly through dimers containing OSMR and gp130 and shows limited activity through mouse LIFR. Despite their structural similarity, neither human nor mouse OSM signal through the other species' OSMR. The molecular basis for such species-specific signaling, however, remains poorly understood. To identify key molecular features of OSM that determine receptor activation in humans and mice, we generated chimeric mouse-human cytokines. Replacing regions within binding site III of murine OSM with the human equivalents showed that the cytokine's AB loop was critical for receptor selection. Substitutions of individual amino acids within this region demonstrated that residues Asn-37, Thr-40, and Asp-42 of the murine cytokine were responsible for limited LIFR activation and absence of human OSMR/LIFR signaling. In human OSM, Lys-44 appeared to be the main residue preventing mouse OSMR activation. Our data reveal that individual amino acids within the AB loop of OSM determine species-specific activities. These mutations might reflect a key step in the evolutionary process of this cytokine, in which receptor promiscuity gives way to ligand-receptor specialization.
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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.