GO:0004924 oncostatin-M receptor activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0004924 (oncostatin-M receptor activity) is a molecular function defined as combining with oncostatin-M and transmitting the signal across the membrane to initiate a change in cell activity.
• The receptor is a heteromeric complex of gp130 (IL6ST) and OSMR, shared with other IL-6 family cytokines, which determines signaling specificity.
• Oncostatin M receptor signaling drives JAK/STAT, MAPK and SMAD-dependent transcriptional programs in fibroblasts, immune cells, neurons and cardiomyocytes.
• Dysregulated oncostatin-M receptor activity is implicated in radiation-induced heart fibrosis, glioblastoma mesenchymal transition, cancer cachexia and skin inflammation.
• CRISPR knockout, point-mutation, knock-in and overexpression models are essential to dissect ligand-receptor specificity and downstream effector pathways.
• EDITGENE provides end-to-end CRISPR cell model and library screening services to study oncostatin-M receptor activity in disease-relevant contexts.
Description
Oncostatin-M receptor activity (GO:0004924) is a molecular function that enables a cell to bind the cytokine oncostatin M and convert that binding event into an intracellular signal. This activity is mediated by a heteromeric receptor complex composed of the shared signal-transducing subunit gp130 (IL6ST) and the ligand-specific subunit OSMR, a member of the IL-6 cytokine family receptor group. Because the same gp130 subunit is used by several cytokines, the oncostatin-M receptor complex provides a paradigm for understanding how ligand-specific receptor subunits confer signaling specificity. Researchers study GO:0004924 to dissect cytokine-driven inflammation, tissue remodeling and tumor progression, and to identify therapeutic entry points in diseases where oncostatin M signaling is dysregulated. The receptor is expressed in diverse cell types including fibroblasts, immune cells, sensory neurons and cardiomyocytes, where it controls context-dependent transcriptional programs. This article integrates the QuickGO definition with verified PubMed literature to summarize the mechanism, key genes, disease links and experimental methods relevant to oncostatin-M receptor activity.
oncostatin-M receptor activity At A Glance
| GO ID | GO:0004924 |
|---|---|
| GO term | oncostatin-M receptor activity |
| Ontology | molecular_function |
| Synonym | None listed in QuickGO |
| Definition | Combining with oncostatin-M and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity. |
| Major function | Cytokine binding and transmembrane signal transduction for oncostatin M |
| Receptor subunits | OSMR (ligand-specific) and IL6ST/gp130 (shared signal-transducing) |
| Downstream pathways | JAK/STAT, MAPK, SMAD-dependent transcription |
| Cellular contexts | Fibroblasts, immune cells, sensory neurons, cardiomyocytes |
What Is GO:0004924?
In simple terms, oncostatin-M receptor activity is the ability of a cell-surface receptor complex to catch the cytokine oncostatin M and pass a signal into the cell. According to the QuickGO definition, this molecular function is defined as combining with oncostatin-M and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity. It is a molecular_function term (GO:0004924) with no listed synonyms. The activity requires both ligand binding and signal transduction, distinguishing it from passive binding proteins. The receptor complex typically comprises OSMR and gp130 (IL6ST), and ligand engagement activates associated JAK kinases and downstream STAT, MAPK and SMAD pathways.
Why Is oncostatin-M receptor activity Important in Cell Biology?
Oncostatin-M receptor activity is important because it translates a single cytokine cue into diverse cell-type-specific responses that shape inflammation, tissue repair, fibrosis and tumor biology. Because the receptor complex is a node where multiple signaling pathways converge, its activity is a critical determinant of whether cells adopt protective, reparative or pathological states. Understanding GO:0004924 at molecular resolution supports target validation for inflammatory diseases, cancer and cardiac fibrosis, and enables rational design of biologics or small molecules that modulate this receptor.
• Controls JAK/STAT, MAPK and SMAD signaling in fibroblasts, immune cells and neurons.
• Drives radiation-induced heart fibrosis through SMAD4 regulation in fibroblasts.
• Promotes mesenchymal-like transitions in glioblastoma via cancer-immune cell interactions.
• Activates vagal sensory neurons in allergy-related neuroimmune circuits.
• Contributes to skin inflammation, immunity and tumorigenesis.
• Plays context-dependent roles in cardiomyocyte protection, regeneration and failure.
• Linked to cancer cachexia through EDA2R-NIK signaling crosstalk.
• Provides a shared gp130-dependent signaling node with other IL-6 family cytokines.
• Represents a therapeutic target in inflammatory diseases and cancer.
• Requires precise CRISPR models to separate ligand-specific from shared subunit functions.
What Happens During oncostatin-M receptor activity?
Ligand recognition and receptor assembly
In simple terms: Oncostatin M binds to its specific receptor subunit, which then recruits a shared signaling partner.
Oncostatin M is a member of the IL-6 cytokine family that binds the ligand-specific OSMR subunit. Ligand engagement promotes assembly of a heteromeric receptor complex containing OSMR and the shared signal-transducing subunit gp130 (IL6ST). This assembly is the first step in oncostatin-M receptor activity and determines signaling specificity relative to other IL-6 family cytokines that also use gp130.
JAK activation and STAT phosphorylation
In simple terms: Once the receptor partners are together, enzymes called JAKs add phosphate tags to STAT proteins, which then move to the nucleus.
Receptor complex formation brings associated JAK kinases into proximity, enabling trans-phosphorylation and activation. Activated JAKs phosphorylate STAT transcription factors, which dimerize and translocate to the nucleus to regulate target gene expression. This JAK/STAT axis is a canonical output of oncostatin-M receptor activity in multiple cell types.
MAPK and SMAD pathway integration
In simple terms: The receptor also switches on other signaling routes, including MAPK and SMAD, which fine-tune the cellular response.
Beyond JAK/STAT, oncostatin-M receptor activity engages MAPK cascades and SMAD-dependent transcription. In fibroblasts, oncostatin M/OSMR signaling regulates SMAD4 to induce radiation-induced heart fibrosis, demonstrating integration between cytokine receptor and TGF-beta-related pathways. This pathway crosstalk explains why the same receptor activity can produce distinct outcomes in different tissues.
Cell-type-specific transcriptional and phenotypic outcomes
In simple terms: The final result depends on the cell: fibroblasts may become fibrotic, cancer cells may change state, and neurons may fire signals.
In glioblastoma, interactions between cancer cells and immune cells drive transitions to mesenchymal-like states through oncostatin M receptor signaling. In allergy models, basophils activate oncostatin M receptor-expressing vagal sensory neurons, linking immune signals to neuronal activation. In the heart, oncostatin M and its receptor complexes have context-dependent roles in cardiomyocyte protection, regeneration and failure. These examples show that GO:0004924 is a hub whose phenotypic output is dictated by cell type and microenvironment.
Key Genes Involved in GO:0004924 oncostatin-M receptor activity
The following genes encode the ligand, receptor subunits and principal downstream effectors that define oncostatin-M receptor activity and its cellular outputs.
| Gene | Major Role | Research Relevance |
|---|---|---|
| OSM | Ligand that binds and activates the receptor | Central to studying ligand-dependent receptor activation |
| OSMR | Ligand-specific receptor subunit | Determines oncostatin M specificity and is a key KO target |
| IL6ST | Shared signal-transducing subunit gp130 | Required for JAK/STAT activation and shared with other cytokines |
| JAK1 | Kinase that phosphorylates STATs downstream of receptor | Effector of receptor-proximal signaling |
| JAK2 | Kinase contributing to receptor signaling | Effector of receptor-proximal signaling |
| STAT1 | Transcription factor activated downstream | Readout of receptor activity |
| STAT3 | Transcription factor activated downstream | Major mediator of oncostatin M responses |
| SMAD4 | Integrates SMAD-dependent transcription | Required for radiation-induced heart fibrosis |
| MAPK1 | MAPK pathway effector | Contributes to non-STAT signaling outputs |
| MAPK3 | MAPK pathway effector | Contributes to non-STAT signaling outputs |
| EDA2R | Receptor linked to cachexia signaling crosstalk | Relevant to muscle atrophy biology |
| NIK | Kinase in non-canonical NF-kB signaling | Mediates EDA2R-driven muscle atrophy |
| IL6 | Related IL-6 family cytokine | Context for shared gp130 signaling |
| LIF | Related IL-6 family cytokine | Context for shared gp130 signaling |
| CNTF | Related IL-6 family cytokine | Context for shared gp130 signaling |
| CTF1 | Related IL-6 family cytokine | Context for shared gp130 signaling |
| CLCF1 | Related IL-6 family cytokine | Context for shared gp130 signaling |
How Is oncostatin-M receptor activity Regulated?
Oncostatin-M receptor activity is regulated at multiple levels. Ligand availability controls receptor engagement, and the shared gp130 subunit is used by several IL-6 family cytokines, creating competition and crosstalk that shape signaling output. Receptor-proximal JAK/STAT activation is balanced by MAPK and SMAD pathway inputs, and in fibroblasts SMAD4 is required for oncostatin M-driven radiation-induced heart fibrosis. In the heart, oncostatin M and its receptor complexes have context-dependent effects on cardiomyocyte protection, regeneration and failure, indicating that tissue-specific regulators modulate the pathway. In cancer cachexia, EDA2R-NIK signaling intersects with muscle atrophy programs, illustrating crosstalk between related cytokine receptor systems. In skin, oncostatin M and its receptor are regulated during immunity, inflammation and tumorigenesis, with distinct outcomes depending on microenvironment.
oncostatin-M receptor activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| OSMR | Radiation-induced heart fibrosis | Fibroblast-specific OSMR knockout in mouse models |
| SMAD4 | Radiation-induced heart fibrosis | SMAD4 point-mutation or knockout fibroblasts |
| OSMR | Glioblastoma mesenchymal transition | Co-culture of glioblastoma cells with immune cells |
| OSMR | Allergic neuroimmune activation | Vagal sensory neuron activation assays |
| EDA2R | Cancer cachexia and muscle atrophy | Muscle atrophy models with EDA2R-NIK perturbation |
Radiation-induced heart fibrosis
Oncostatin M/oncostatin M receptor signaling induces radiation-induced heart fibrosis by regulating SMAD4 in fibroblasts. This links GO:0004924 directly to a clinically important complication of thoracic radiotherapy, where fibroblast activation and extracellular matrix deposition impair cardiac function. The receptor therefore represents a candidate target for antifibrotic intervention in radiation-exposed patients.
Glioblastoma progression
Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma, a process in which oncostatin M receptor signaling participates. Mesenchymal-like states are associated with therapy resistance and aggressive behavior, making GO:0004924 relevant to tumor microenvironment-directed strategies.
Allergic neuroimmune activation
Basophils activate oncostatin M receptor-expressing vagal sensory neurons, connecting allergic immune responses to sensory neuronal activation. This positions oncostatin-M receptor activity as a mediator of neuroimmune crosstalk in allergy and itch-related circuits.
Cancer cachexia and muscle atrophy
EDA2R-NIK signaling promotes muscle atrophy linked to cancer cachexia, a process that intersects with cytokine receptor signaling networks that include oncostatin M family pathways. Understanding how GO:0004924-related signaling integrates with cachexia pathways may inform combination strategies for muscle preservation in cancer patients.
From oncostatin-M receptor activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is OSMR required for oncostatin M signaling? | OSMR knockout cell line |
| Does a specific OSMR residue control ligand binding? | OSMR point-mutation knock-in |
| Can a tagged OSMR track receptor trafficking? | Tagged OSMR knock-in |
| Does OSMR overexpression sensitize cells to oncostatin M? | OSMR overexpression cell line |
| Which downstream genes respond to receptor activation? | STAT3/SMAD4 knockout with RNA-seq |
| Does receptor activity drive fibrosis in fibroblasts? | Fibroblast knockout in radiation fibrosis models |
How to Study the oncostatin-M receptor activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNA-seq | Transcriptional changes after receptor activation | Identify downstream target genes |
| Phospho-Western blot | STAT and MAPK activation status | Validate receptor signaling competence |
| Co-culture assays | Cancer-immune cell interactions | Model glioblastoma mesenchymal transition |
| Neuronal activation assays | Sensory neuron firing responses | Study allergy neuroimmune circuits |
| Fibrosis histology | Collagen deposition and tissue remodeling | Assess radiation-induced heart fibrosis |
| Muscle atrophy assays | Muscle fiber size and atrophy markers | Study cancer cachexia pathways |
| CRISPR screening | Gene requirements for receptor-dependent phenotypes | Discover modifiers of oncostatin M signaling |
Transcriptomic profiling of receptor activation
RNA-seq after oncostatin M stimulation of wild-type and receptor-mutant cells identifies transcriptional programs downstream of GO:0004924. Comparing OSMR knockout, IL6ST knockout and SMAD4 knockout cells reveals which outputs depend on specific receptor subunits and effectors.
Phospho-signaling assays
Western blotting for phosphorylated STAT1, STAT3 and MAPK measures receptor-proximal signaling competence in response to ligand. These assays are used to validate that CRISPR-engineered receptor variants retain or lose signal transduction.
Co-culture and neuroimmune activation assays
Co-culture of cancer cells with immune cells models the microenvironmental interactions that drive mesenchymal-like transitions through oncostatin M receptor signaling. Vagal sensory neuron activation assays measure neuronal responses to basophil-derived signals in allergy models.
In vivo fibrosis and cachexia models
Radiation-induced heart fibrosis models assess fibroblast-specific receptor and SMAD4 contributions to cardiac remodeling. Cancer cachexia models evaluate muscle atrophy pathways linked to EDA2R-NIK signaling.
How CRISPR Can Be Used to Study GO:0004924 oncostatin-M receptor activity
Knockout
CRISPR knockout of OSMR or IL6ST abolishes oncostatin-M receptor activity and is used to test whether a phenotype depends on this molecular function. Fibroblast-specific knockout has been used to show that oncostatin M/OSMR signaling drives radiation-induced heart fibrosis through SMAD4. Knockout of downstream effectors such as STAT3 or SMAD4 separates receptor-proximal from distal requirements.
Point Mutation
Point mutations in OSMR or IL6ST can disrupt ligand-binding interfaces or JAK-binding motifs while preserving protein expression, allowing precise structure-function mapping of GO:0004924. Such models help distinguish loss of binding from loss of signal transduction.
Knock-in
Tagged knock-in of OSMR or IL6ST enables tracking of receptor localization, complex assembly and trafficking in live cells. Knock-in of disease-associated variants can test whether specific alleles alter receptor activity in relevant cell types.
Overexpression
Overexpression of OSMR or oncostatin M sensitizes cells to ligand and amplifies downstream JAK/STAT, MAPK and SMAD outputs. Overexpression models are useful for gain-of-function studies in cardiomyocytes, fibroblasts and cancer cells where receptor levels shape phenotypic outcomes.
How EDITGENE Supports oncostatin-M receptor activity Research
Researchers studying oncostatin-M receptor activity-related genes often need to determine whether a candidate gene is causally involved in ligand binding, receptor assembly or downstream signaling, and CRISPR-based cell models provide the most direct way to establish causality. EDITGENE supports these studies with validated knockout, point-mutation, knock-in, overexpression and library screening services tailored to cytokine receptor biology.
Contact EDITGENE today to design your custom CRISPR model for oncostatin-M receptor activity research.
Frequently Asked Questions About oncostatin-M receptor activity
What is oncostatin-M receptor activity?
Oncostatin-M receptor activity (GO:0004924) is a molecular function in which a cell-surface receptor complex binds oncostatin M and transmits a signal across the membrane to change cell activity.
What genes are involved in oncostatin-M receptor activity?
Key genes include OSM (ligand), OSMR (ligand-specific subunit), IL6ST/gp130 (shared signal-transducing subunit), and downstream effectors such as JAK1, JAK2, STAT1, STAT3, SMAD4, MAPK1 and MAPK3.
What is the GO ID for oncostatin-M receptor activity?
The Gene Ontology ID is GO:0004924, classified under molecular_function.
Which diseases are linked to oncostatin-M receptor activity?
It has been linked to radiation-induced heart fibrosis, glioblastoma mesenchymal transition, allergic neuroimmune activation, skin inflammation and cancer cachexia.
How does oncostatin M receptor signaling work?
Oncostatin M binds OSMR, which assembles with gp130/IL6ST to activate JAK kinases, STAT transcription factors, MAPK cascades and SMAD-dependent transcription.
What is the difference between OSMR and gp130?
OSMR is the ligand-specific subunit that binds oncostatin M, while gp130 (IL6ST) is a shared signal-transducing subunit used by multiple IL-6 family cytokines.
How can I study oncostatin-M receptor activity in the lab?
Common approaches include CRISPR knockout of OSMR or IL6ST, phospho-STAT Western blotting, RNA-seq, co-culture assays and in vivo fibrosis or cachexia models.
Is oncostatin M receptor activity involved in heart disease?
Yes, oncostatin M/OSMR signaling induces radiation-induced heart fibrosis by regulating SMAD4 in fibroblasts, and receptor complexes have context-dependent roles in cardiomyocyte protection, regeneration and failure.
Can CRISPR be used to model oncostatin-M receptor activity?
Yes, CRISPR knockout, point-mutation, knock-in and overexpression models are widely used to dissect receptor subunit requirements and downstream signaling.
What cell types express oncostatin M receptors?
Oncostatin M receptor activity has been studied in fibroblasts, immune cells, glioblastoma cells, vagal sensory neurons and cardiomyocytes.
Conclusion
Oncostatin-M receptor activity (GO:0004924) is a molecular function that converts oncostatin M binding into JAK/STAT, MAPK and SMAD-dependent cellular responses, with critical roles in fibrosis, cancer, neuroimmune activation and cardiac biology. Because the receptor complex shares gp130 with other IL-6 family cytokines, precise genetic models are required to separate ligand-specific from shared signaling contributions. CRISPR-based knockout, point-mutation, knock-in and overexpression approaches, combined with transcriptomic and phospho-signaling readouts, provide a robust framework for dissecting this pathway in disease-relevant contexts. EDITGENE offers integrated cell model and screening services to accelerate research on oncostatin-M receptor activity and its therapeutic potential.
References
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- 4. Bruce AG et al.. 1992. Oncostatin M.. Prog Growth Factor Res 4(2):157-70 PMID: 1338575
- 5. Jones SA et al.. 2018. Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer.. Nat Rev Immunol 18(12):773-789 PMID: 30254251
- 6. Zou Y et al.. 2026. The multifaceted roles of oncostatin M and its receptor in skin immunity, inflammation, and tumorigenesis.. J Invest Dermatol 146(6):1486-1500 PMID: 41505783
- 7. Kubin T et al.. 2022. The Role of Oncostatin M and Its Receptor Complexes in Cardiomyocyte Protection, Regeneration, and Failure.. Int J Mol Sci 23(3) PMID: 35163735
- 8. Bilgic SN et al.. 2023. EDA2R-NIK signalling promotes muscle atrophy linked to cancer cachexia.. Nature 617(7962):827-834 PMID: 37165186
