GO:0005900 type I oncostatin-M receptor complex: Components, Assembly and Research Methods, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0005900 describes the type I oncostatin-M receptor complex, a heterodimeric cell-surface receptor for the cytokine oncostatin M (OSM) composed of gp130 (IL6ST) and OSMR-beta.
• The complex is a member of the IL-6 family cytokine receptor superfamily and signals through gp130-dependent JAK/STAT, MAPK and PI3K pathways.
• Structural studies have resolved the complete extracellular assembly of the type I OSM receptor complex, revealing how OSM bridges gp130 and OSMR-beta.
• Dysregulated OSM signaling through this receptor has been implicated in cardiomyocyte protection and failure, inflammatory skin disease, and multiple cancers.
• OSMR-beta mutations cause familial primary localized cutaneous amyloidosis, directly linking the receptor to human genetic disease.
• CRISPR-based knockout, knock-in and overexpression models enable causal dissection of type I OSM receptor complex function in health and disease.
Description
The type I oncostatin-M receptor complex (GO:0005900) is a heterodimeric cytokine receptor that mediates cellular responses to oncostatin M (OSM), a pleiotropic interleukin-6 (IL-6) family cytokine. In humans, the complex is assembled from two distinct transmembrane proteins: the shared signal-transducing subunit gp130 (encoded by IL6ST) and the OSM-specific receptor subunit OSMR-beta (encoded by OSMR). This receptor configuration distinguishes the type I OSM receptor from the type II OSM receptor, which uses gp130 paired with the leukemia inhibitory factor receptor (LIFR). The type I complex is therefore the principal route through which OSM exerts OSMR-beta-dependent effects in cells that lack or express low levels of LIFR. Researchers study GO:0005900 because OSM signaling influences a remarkably broad set of biological processes, including cardiomyocyte survival and regeneration, hepatic acute-phase responses, mammary epithelial proliferation, and inflammatory skin homeostasis. The receptor complex is also a therapeutic target: gp130 antagonism has been shown to enhance right ventricular function in a large-animal model, underscoring the translational relevance of this signaling axis. Structural characterization of the complete extracellular assemblies of the type I and type II OSM receptor complexes has provided a molecular blueprint for how OSM engages gp130 and OSMR-beta to initiate signaling. From a genomics and cell-engineering perspective, GO:0005900 provides a defined functional entity for interrogating cytokine receptor biology. Because the complex is built from two gene products, IL6ST and OSMR, it is particularly amenable to CRISPR-based perturbation, including knockout of either subunit, knock-in of tagged or mutant alleles, and overexpression of wild-type or disease-associated variants. Such models are essential for determining which downstream outputs, such as STAT3 phosphorylation or proliferation, depend specifically on the type I receptor rather than on shared gp130-containing complexes.
type I oncostatin-M receptor complex At A Glance
| GO ID | GO:0005900 |
|---|---|
| GO term | type I oncostatin-M receptor complex |
| Ontology | cellular_component |
| Synonym | oncostatin-M receptor complex |
| Definition | A heterodimeric receptor for the cytokine oncostatin-M (OSM). In humans the receptor complex is made up of the gene products gp130 and OSMR-beta. |
| Major function | Binds oncostatin M and initiates intracellular signaling through gp130-associated JAK/STAT, MAPK and PI3K pathways. |
| Subunit composition | Heterodimer of gp130 (IL6ST) and OSMR-beta (OSMR). |
| Cytokine family | IL-6 family cytokine receptor complex. |
| Related receptor | Type II OSM receptor complex (gp130 plus LIFR). |
What Is GO:0005900?
GO:0005900, the type I oncostatin-M receptor complex, is a heterodimeric cell-surface receptor for the cytokine oncostatin-M (OSM). In humans, the receptor complex is composed of the gene products gp130 and OSMR-beta. It is annotated as a cellular component and represents the OSM-specific receptor assembly that is distinct from the type II OSM receptor, which uses gp130 paired with LIFR.
Why Is type I oncostatin-M receptor complex Important in Cell Biology?
The type I oncostatin-M receptor complex is important because it defines the OSM-specific signaling route that controls context-dependent programs of cell survival, proliferation, differentiation and inflammation. Unlike gp130, which is shared by many cytokines, OSMR-beta confers specificity for OSM and related cytokines, making the type I complex a focal point for understanding how a single cytokine can elicit distinct outputs in different tissues. Its relevance spans cardiovascular biology, where OSM signaling has been linked to cardiomyocyte protection and failure, and gp130 antagonism can enhance right ventricular function; cancer biology, where OSM receptor expression and function regulate proliferation of normal and malignant mammary epithelial cells; and human genetics, where OSMR-beta mutations cause familial primary localized cutaneous amyloidosis. The complex is also a template for structure-function studies of cytokine receptor assembly, as recent work has resolved the complete extracellular architecture of both type I and type II OSM receptor complexes.
• Defines the OSM-specific receptor route that is distinct from the shared gp130/LIFR type II receptor.
• Controls JAK/STAT, MAPK and PI3K signaling downstream of OSM binding.
• Implicated in cardiomyocyte protection, regeneration and heart failure.
• GP130 antagonism enhances porcine right ventricular function, highlighting therapeutic potential.
• OSMR-beta mutations cause familial primary localized cutaneous amyloidosis.
• Regulates proliferation of normal and malignant mammary epithelial cells.
• Provides a structural model for cytokine receptor heterodimer assembly.
• Serves as a target for CRISPR knockout, knock-in and overexpression studies.
• Relevant to inflammatory skin disease and pruritus-related cytokine networks.
• Enables dissection of OSM versus LIF signaling in cells expressing both receptor types.
Structure and Composition of type I oncostatin-M receptor complex
gp130 (IL6ST) subunit
In simple terms: gp130 is the shared signaling subunit that many IL-6 family cytokines use.
gp130, encoded by IL6ST, is the common signal-transducing subunit of the type I oncostatin-M receptor complex. It is a type I transmembrane glycoprotein that associates with JAK kinases and provides the intracellular docking sites required for STAT activation. In the type I OSM receptor, gp130 pairs with OSMR-beta rather than with LIFR, and this pairing determines the specificity of downstream signaling.
OSMR-beta (OSMR) subunit
In simple terms: OSMR-beta is the subunit that makes the receptor specific for oncostatin M.
OSMR-beta, encoded by OSMR, is the OSM-specific subunit of the type I receptor complex. It is a transmembrane protein that binds OSM and, together with gp130, forms the heterodimeric receptor. OSMR-beta expression is regulated in a cell-type-specific manner; for example, type II OSM receptor expression in lung-derived epithelial cells is modulated by environmental cues, and OSMR-beta is the subunit whose mutations underlie familial primary localized cutaneous amyloidosis.
Oncostatin M ligand and receptor assembly
In simple terms: Oncostatin M is the cytokine that brings the two receptor subunits together.
Oncostatin M (OSM) is the cytokine ligand that bridges gp130 and OSMR-beta to assemble the type I receptor complex. Structural studies of the complete extracellular assemblies of type I and type II OSM receptor complexes have revealed how OSM engages both subunits to form a signaling-competent heterodimer. This assembly is a prerequisite for recruitment and activation of JAK kinases and subsequent phosphorylation of downstream STAT proteins.
Membrane topology and signaling platform
In simple terms: The receptor sits in the cell membrane and turns an outside signal into an inside response.
The type I oncostatin-M receptor complex is a cell-surface assembly in which the extracellular domains of gp130 and OSMR-beta bind OSM, while their intracellular domains provide the platform for JAK/STAT, MAPK and PI3K signaling. This membrane topology allows the complex to convert an extracellular cytokine signal into changes in gene expression, proliferation and survival.
Distinction from the type II OSM receptor
In simple terms: A second receptor uses a different partner subunit, LIFR, instead of OSMR-beta.
The type II oncostatin-M receptor complex uses gp130 paired with the leukemia inhibitory factor receptor (LIFR) rather than OSMR-beta. This distinction is functionally important because the two complexes can mediate overlapping but non-identical downstream responses, and cells may express one or both receptor types depending on tissue context. Studies of type II receptor expression in lung-derived epithelial cells illustrate how the two receptor systems can be differentially regulated.
Key Genes Involved in GO:0005900 type I oncostatin-M receptor complex
The following genes and proteins are the principal components and regulators of the type I oncostatin-M receptor complex and its signaling axis.
| Gene | Major Role | Research Relevance |
|---|---|---|
| IL6ST (gp130) | Shared signal-transducing subunit of the type I OSM receptor complex | Knockout or point mutation to dissect JAK/STAT-dependent outputs |
| OSMR (OSMR-beta) | OSM-specific subunit that binds oncostatin M | Disease variant modeling and receptor-specific knockout |
| OSM | Cytokine ligand that assembles the receptor complex | Overexpression or knockout to study autocrine/paracrine signaling |
| LIFR | Subunit of the type II OSM receptor complex | Comparative studies of type I versus type II receptor signaling |
| JAK1 | Kinase recruited to gp130 to initiate signaling | Point mutation to block kinase activity |
| JAK2 | Kinase associated with cytokine receptor signaling | Knockout to test JAK dependence |
| STAT3 | Transcription factor activated downstream of the receptor | Reporter and knockout models for transcriptional output |
| STAT1 | Transcription factor activated by OSM signaling | Knockout to separate STAT1 versus STAT3 effects |
| SOCS3 | Negative regulator of cytokine receptor signaling | Overexpression to suppress receptor output |
| PIK3CA | PI3K catalytic subunit in receptor signaling | Knockout to test PI3K dependence |
| MAPK1 (ERK2) | MAPK pathway kinase downstream of the receptor | Point mutation to block MAPK signaling |
| MAPK3 (ERK1) | MAPK pathway kinase downstream of the receptor | Knockout to test ERK dependence |
| IL6 | Related IL-6 family cytokine sharing gp130 | Comparative ligand studies |
| IL31 | Cytokine related to OSM signaling in inflammation | Knockout to study inflammatory skin biology |
| OSMR-beta variants | Disease-associated mutations in OSMR | Knock-in of patient variants for amyloidosis modeling |
| gp130 antagonists | Experimental tools that block gp130 signaling | Used to test receptor complex inhibition in vivo |
How Is type I oncostatin-M receptor complex Regulated?
The type I oncostatin-M receptor complex is regulated at multiple levels. Receptor expression is controlled in a cell-type-specific manner, as shown by studies of type II OSM receptor expression in lung-derived epithelial cells. Signaling downstream of the complex is subject to negative feedback by SOCS proteins, which dampen JAK/STAT activation. In addition, the availability of the shared gp130 subunit and the relative abundance of OSMR-beta versus LIFR determine whether OSM signals through the type I or type II receptor complex. Pharmacological and genetic tools such as gp130 antagonists can further modulate receptor output, as demonstrated by enhanced porcine right ventricular function upon gp130 antagonism.
type I oncostatin-M receptor complex and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| OSMR | Familial primary localized cutaneous amyloidosis | Knock-in of patient OSMR-beta mutations in keratinocytes |
| IL6ST (gp130) | Cardiac dysfunction and heart failure | Cardiomyocyte-specific knockout or gp130 antagonism |
| OSM | Mammary epithelial proliferation and cancer | Overexpression or knockout in mammary epithelial cells |
| IL31 | Inflammatory skin disease and pruritus | Knockout or overexpression in skin models |
| STAT3 | Cytokine-driven inflammation and cancer | Point mutation or knockout to block downstream signaling |
Familial primary localized cutaneous amyloidosis
Mutations in OSMR-beta underlie familial primary localized cutaneous amyloidosis, directly linking the type I oncostatin-M receptor complex to a Mendelian skin disease. This connection makes the receptor a model for studying how altered cytokine receptor function contributes to protein deposition and cutaneous pathology.
Cardiovascular disease and heart failure
Oncostatin M and its receptor complexes have been implicated in cardiomyocyte protection, regeneration and failure. Experimental gp130 antagonism enhances porcine right ventricular function, suggesting that modulating this receptor axis may have therapeutic potential in heart disease.
Cancer and mammary epithelial proliferation
Oncostatin M-specific receptor expression and function regulate proliferation of normal and malignant mammary epithelial cells, indicating a role for the type I receptor complex in breast cancer biology. Dysregulated OSM signaling may therefore influence tumor cell growth and survival.
Inflammatory skin disease and pruritus
OSM-related cytokine networks, including IL-31, connect inflammatory signaling to pruritus and cancer. Because the type I OSM receptor complex mediates OSM-specific responses, it is relevant to inflammatory skin conditions and itch-associated pathways.
From type I oncostatin-M receptor complex-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does OSMR-beta mediate OSM-specific signaling? | OSMR knockout cell line |
| Is gp130 required for type I receptor signaling? | IL6ST knockout or point mutation |
| Do disease-associated OSMR variants alter receptor function? | Knock-in of patient mutations |
| Where is the receptor complex localized in cells? | Tagged knock-in of OSMR or IL6ST |
| Does overexpression of OSM drive proliferation? | OSM overexpression in mammary epithelial cells |
| Can gp130 antagonism improve cardiac function? | In vivo gp130 antagonist model |
How to Study the type I oncostatin-M receptor complex Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Cryo-EM / structural biology | Receptor complex assembly and ligand binding | Understanding type I versus type II OSM receptor architecture |
| CRISPR knockout | Loss-of-function of IL6ST or OSMR | Testing receptor subunit requirement |
| CRISPR knock-in | Disease variant expression | Modeling OSMR-beta mutations |
| Overexpression | Gain-of-function of OSM or receptor subunits | Studying proliferation and signaling |
| Phospho-STAT immunoblot | JAK/STAT pathway activation | Measuring immediate receptor signaling |
| RNA-seq | Transcriptional changes downstream of receptor | Defining OSM-specific gene programs |
| In vivo gp130 antagonism | Cardiac function and receptor blockade | Translational cardiovascular studies |
| Comparative receptor expression assays | Type I versus type II receptor levels | Cell-type-specific regulation studies |
Structural biology and receptor assembly
Structural studies of the complete extracellular assemblies of type I and type II OSM receptor complexes provide high-resolution insight into how OSM bridges gp130 and OSMR-beta. These methods are essential for understanding the molecular basis of receptor specificity and for designing inhibitors.
CRISPR knockout and knock-in models
CRISPR-based knockout of IL6ST or OSMR allows causal testing of receptor subunit requirements, while knock-in of disease-associated OSMR variants enables modeling of familial primary localized cutaneous amyloidosis. These approaches are complemented by overexpression of wild-type or mutant receptor components.
Signaling assays and transcriptomics
Phospho-STAT, MAPK and PI3K assays measure immediate downstream signaling from the type I receptor complex. RNA-seq and reporter assays can define transcriptional outputs, while comparative studies of type I versus type II receptor signaling help separate OSMR-beta-specific effects.
In vivo and functional models
Animal models and pharmacological tools such as gp130 antagonists allow assessment of receptor complex function in cardiovascular and inflammatory contexts. These models are critical for translating cell-based findings into disease relevance.
How CRISPR Can Be Used to Study GO:0005900 type I oncostatin-M receptor complex
Knockout
CRISPR knockout of IL6ST or OSMR eliminates the type I oncostatin-M receptor complex and allows researchers to test which OSM-induced responses depend on this specific receptor. Such models are foundational for distinguishing OSMR-beta-dependent signaling from LIFR-dependent type II receptor signaling.
Point Mutation
Point mutations can be introduced into IL6ST or OSMR to disrupt specific signaling motifs, such as JAK-binding sites, without removing the entire protein. This approach enables fine mapping of the molecular determinants of receptor function.
Knock-in
Knock-in of disease-associated OSMR-beta mutations, such as those causing familial primary localized cutaneous amyloidosis, allows modeling of human genetic disease in relevant cell types. Tagged knock-in of receptor subunits also supports localization and interaction studies.
Overexpression
Overexpression of OSM, OSMR-beta or gp130 can amplify receptor signaling and is useful for studying proliferation and survival outputs in mammary epithelial and other cell types. Overexpression models complement loss-of-function studies to establish causality.
How EDITGENE Supports type I oncostatin-M receptor complex Research
Researchers studying type I oncostatin-M receptor complex-related genes often need to determine whether a candidate gene is causally involved in receptor assembly, signaling or disease. EDITGENE provides the CRISPR tools and cell models required to move from correlation to causation.
Contact EDITGENE today to design your custom CRISPR model for type I oncostatin-M receptor complex research.
Frequently Asked Questions About type I oncostatin-M receptor complex
What is the type I oncostatin-M receptor complex?
It is a heterodimeric cell-surface receptor for oncostatin M composed of gp130 and OSMR-beta, annotated as GO:0005900.
What genes are involved in the type I oncostatin-M receptor complex?
The principal genes are IL6ST (gp130) and OSMR (OSMR-beta), with downstream signaling involving JAK and STAT genes.
What is the difference between type I and type II oncostatin-M receptors?
The type I receptor uses gp130 and OSMR-beta, while the type II receptor uses gp130 and LIFR.
What diseases are associated with the type I oncostatin-M receptor complex?
OSMR-beta mutations cause familial primary localized cutaneous amyloidosis, and the receptor is implicated in heart failure and cancer.
How does oncostatin M signal through its receptor?
OSM bridges gp130 and OSMR-beta, activating JAK/STAT, MAPK and PI3K pathways.
What is the role of OSMR-beta in disease?
OSMR-beta mutations underlie familial primary localized cutaneous amyloidosis and OSMR-beta expression regulates mammary epithelial proliferation.
Can CRISPR be used to study the type I oncostatin-M receptor complex?
Yes, CRISPR knockout, knock-in and overexpression models are widely used to dissect receptor subunit function.
What cell models are available for OSM receptor research?
Knockout, point mutation, knock-in and overexpression cell models for IL6ST, OSMR and downstream signaling genes are available.
Is gp130 the same as IL6ST?
Yes, gp130 is the protein product of the IL6ST gene and is the shared signaling subunit of the type I OSM receptor complex.
Why is the type I oncostatin-M receptor complex important in cardiovascular disease?
OSM signaling has been linked to cardiomyocyte protection and failure, and gp130 antagonism enhances right ventricular function.
Conclusion
The type I oncostatin-M receptor complex (GO:0005900) is a defined heterodimeric cytokine receptor composed of gp130 and OSMR-beta that mediates oncostatin M-specific signaling. Its structural architecture, downstream JAK/STAT, MAPK and PI3K pathways, and links to cardiovascular disease, cancer and familial cutaneous amyloidosis make it a compelling target for functional genomics. CRISPR-based knockout, knock-in, point mutation and overexpression models provide the causal evidence needed to translate receptor biology into therapeutic insight.
References
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- 2. Mendelson JB et al.. 2025. GP130 Antagonism Enhances Porcine RV Function.. Circ Res 137(10):1231-1251 PMID: 41031411
- 3. 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
- 4. Akhtar S et al.. 2024. Interleukin-31: The Inflammatory Cytokine Connecting Pruritus and Cancer.. Front Biosci (Landmark Ed) 29(9):312 PMID: 39344323
- 5. Cichy J et al.. 1998. Regulation of the type II oncostatin M receptor expression in lung-derived epithelial cells.. FEBS Lett 429(3):412-6 PMID: 9662460
- 6. Gómez-Lechón MJ. 1999. Oncostatin M: signal transduction and biological activity.. Life Sci 65(20):2019-30 PMID: 10579456
- 7. Arita K et al.. 2008. Oncostatin M receptor-beta mutations underlie familial primary localized cutaneous amyloidosis.. Am J Hum Genet 82(1):73-80 PMID: 18179886
- 8. Liu J et al.. 1998. Oncostatin M-specific receptor expression and function in regulating cell proliferation of normal and malignant mammary epithelial cells.. Cytokine 10(4):295-302 PMID: 9617575
