ArticleThe Journal of biological chemistry2018
The AB loop and D-helix in binding site III of human Oncostatin M (OSM) are required for OSM receptor activation.
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 19 papers.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Oncostatin M as a Multifunctional Regulator of Breast Cancer Progression: Current Insights and Future Therapeutic Avenues.IUBMB life · 2026Review
- Structural Model of the Oncostatin M (OSM)-OSMRβ-gp130 Ternary Complex Reveals Pathways of Allosteric Communication in OSM Signaling.Current medicinal chemistry · 2026Article
- Oncostatin M induces epigenetic reprogramming in renal cell carcinoma-associated endothelial cells.Communications biology · 2025Article
- Elastin-like Recombinamers as a Biotechnological Platform for the Development of Cytokine-Functionalized Materials.ACS omega · 2024Article
- Structures of complete extracellular assemblies of type I and type II Oncostatin M receptor complexes.Nature communications · 2024Article
- Transcriptional and functional consequences of Oncostatin M signaling on young Dnmt3a-mutant hematopoietic stem cells.Experimental hematology · 2024Article
- Role of Oncostatin M in the prognosis of inflammatory bowel disease: A meta-analysis.World journal of gastrointestinal surgery · 2024Article
- The therapeutic potential of targeting Oncostatin M and the interleukin-6 family in retinal diseases: A comprehensive review.Open life sciences · 2024Review
- Oncostatin M-Enriched Small Extracellular Vesicles Derived from Mesenchymal Stem Cells Prevent Isoproterenol-Induced Fibrosis and Enhance Angiogenesis.International journal of molecular sciences · 2023Article
- The clinical relevance of OSM in inflammatory diseases: a comprehensive review.Frontiers in immunology · 2023Review
- Multifaceted oncostatin M: novel roles and therapeutic potential of the oncostatin M signaling in rheumatoid arthritis.Frontiers in immunology · 2023Review
- 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
- Bioactive recombinant human oncostatin M for NMR-based screening in drug discovery.Scientific reports · 2021Article
- Novel mechanism for OSM-promoted extracellular matrix remodeling in breast cancer: LOXL2 upregulation and subsequent ECM alignment.Breast cancer research : BCR · 2021Article
- Oncostatin M promotes infarct repair and improves cardiac function after myocardial infarction.American journal of translational research · 2021Article
- IL-33 Mediates Lung Inflammation by the IL-6-Type Cytokine Oncostatin M.Mediators of inflammation · 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
- The AB loop of oncostatin M (OSM) determines species-specific signaling in humans and mice.The Journal of biological chemistry · 2018Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oncostatin M (OSM) and leukemia inhibitory factor (LIF) are closely related members of the interleukin-6 (IL-6) cytokine family. Both cytokines share a common origin and structure, and both interact through a specific region, termed binding site III, to activate a dimeric receptor complex formed by glycoprotein 130 (gp130) and LIF receptor (LIFR) in humans. However, only OSM activates the OSM receptor (OSMR)-gp130 complex. The molecular features that enable OSM to specifically activate the OSMR are currently unknown. To define specific sequence motifs within OSM that are critical for initiating signaling via OSMR, here we generated chimeric OSM-LIF cytokines and performed alanine-scanning experiments. Replacement of the OSM AB loop within OSM's binding site III with that of LIF abrogated OSMR activation, measured as STAT3 phosphorylation at Tyr-705, but did not compromise LIFR activation. Correspondingly, substitution of the AB loop and D-helix in LIF with their OSM counterparts was sufficient for OSMR activation. The alanine-scanning experiments revealed that residues Tyr-34, Gln-38, Gly-39, and Leu-45 (in the AB loop) and Pro-153 (in the D-helix) had specific roles in activating OSMR but not LIFR signaling, whereas Leu-40 and Cys-49 (in the AB loop), and Phe-160 and Lys-163 (in the D-helix) were required for activation of both receptors. Because most of the key amino acid residues identified here are conserved between LIF and OSM, we concluded that comparatively minor differences in a few amino acid residues within binding site III account for the differential biological effects of OSM and LIF.
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