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IL6ST

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All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

Background

Interleukin-6 signal transducer (IL6ST) referred to as glycoprotein 130, gp130 or CD130 is a approximately 130 kDa type I transmembrane glycoprotein, and was the first identified member of the cytokine receptor superfamily. Biological functionarily, IL6ST is well known as a super promiscuous shared signal-transducing receptor subunit. It is an essential signaling component of at least nine different cytokine receptor complexes that signal through the gp130 receptor include IL-6, IL-11, IL-27, oncostatin M (OSM), leukemia inhibitory factor (LIF), ciliary neurotrophic factor CNTF; cardiotrophin 1 CT-1 and cardiotrophin-like cytokine factor–1 CLCF1. Each cytokine targets a ligand-receptor-specific alpha or beta receptor subunit but all encode protein in the pathway that requires gp130 to transduce cellular signals into the cytoplasm. Cytokine-dependent homodimerization of gp130 or heterodimerization with co-receptors such as LIFR or OSMR for the other family members. Such combinatorial flexibility permits a single receptor subunit to coordinate distinct biological pathways from immune cell differentiation and hepatic acute-phase responses in myeloid cells, to neuronal survival and cardiac homeostasis.

Fig.1 Summary of signalling of IL6ST. (OA Literature)Fig.1 Summary of signalling by cytokines in the IL6-like family.1

IL6ST Protein Function: A Master Signal Integrator at the Crossroads of Immunity and Tissue Homeostasis

IL6ST functionally lies at the nexus of multiple interrelated physiological and pathological areas:

  • JAK-STAT Signal Propagation: Following cytokine binding to IL6ST, the cognate receptor associated with JAK1, JAK2 or TYK2 trans-phosphorylates itself and other neighboring monomers of the receptor leading to generation of multiple phosphotyrosines in the cytoplasmic tail of the receptor generating docking sites for STAT3. These STAT dimers however translocate to the nucleus and induce transcription of regulatory genes that modulate cell proliferation, cell survival, differentiation, and acute-phase protein production. The accuracy of signaling output depends predominantly on the stability and geometry of cytokine-receptor complexes such that even subtle changes in extracellular engagement are transduced into distinct intracellular transcriptional programs.
  • Immune Cell Development and Regulation: IL6ST, also known as gp130, participates in receptor complexes for several cytokines involved in immune-cell differentiation and regulation, including IL-6, IL-11, and IL-27. These cytokines signal through their respective ligand-specific receptor subunits together with gp130, contributing to processes such as T helper 17 (Th17) cell differentiation, germinal center B-cell responses, and regulatory T-cell plasticity. In particular, IL-6 signaling through IL6R/gp130 and downstream STAT3 promotes the differentiation of IL-17-producing Th17 cells while limiting the generation of inducible regulatory T cells.
  • Inflammation and the IL-6 Amplifier: The IL6ST-mediated activation of the transcription factor STAT3 in non-immune cells, together with NF-kB, creates a postive-feedback loop, which we call the IL-6 amplifier (IL-6 Amp). We propose that this mechanism stimulates the local secretion of IL-6 and multiple pro-inflammatory mediators in response to tissue stressors.

IL6ST Membrane Protein Product

We are aware that four features of the six-domain extracellular architecture (extensive glycosylation, required for homodimeric and heterodimeric complex assembly) provide a significant challenge for production. To overcome these, we use flexible expression platforms (mammalian HEK293 cells, insect cell systems and novel lipid-based formulations), to provide precavitation at milligram scale of IL6ST membrane constructs in their correctly folded and fully glycosylated forms that retain both native cytokine-binding affinity and JAK-recruitment competence. We present full-length membrane-bound gp130 plus soluble ectodomain fragments (D1–D6 and D2–D3; as well as disease-associated variants). All preparations are subjected to stringent biophysical validation, for use in structural studies, ligand binding assays and antibody screening.

IL6ST Protein Product

Not finding the membrane protein product you need? Contact us to start your one-stop custom service!

IL6ST Stable Cell Line Product

Reliable, reproducible cellular models are essential to dissect IL6ST biology and evaluate therapeutic candidates. We also offer stable cell lines that have been engineered for over-expression of wildtype or disease-related human, mouse and rat IL6ST (loss-of-function studies with modulated expression of endogenous IL6ST). These platforms have been validated for use in high throughput JAK-STAT reporter assays, Th17 differentiation studies, cytokine signaling pathway characterization and compound screening of gp130 modulators—grouping the experimental reproducibility necessary to yield multi-step data.

IL6ST Stable Cell Line Product

Not finding the stable cell line product you need? Contact us to start your one-stop custom service!

IL6ST Recombinant Antibody Product

We have developed high-affinity recombinant antibodies against IL6ST to fulfil all the rigorous demands in various research applications as a complete package. Unlike conventional polyclonal antibodies, these recombinant technologies allow for the production of highly specific, sensitive and with batch-to-batch constancy. Il6st Recombinant Antibodies: We have validated our recominanant IL6ST antibodies for western blot (WB), ELISA, flow cytometry (FCM), immunofluorescence, ICC (Immunocytochemistry) and IHC in a variety of samples including lymphocyte lysate, hepatocytee preparations from mice with liver injury, inflammatory disease model tissues.

IL6ST Recombinant Antibody Product

Not finding the recombinant antibody product you need? Contact us to start your one-stop custom service!

Product Features

  • High Purity & Activity: High purity and verified integrity for dependable downstream work.
  • Diverse Expression Systems: Choice of expression formats to match routine or specialized projects.
  • Species Reactivity: Products available for human, mouse, pig, and other species.
  • Validated Applications: Application-tested to deliver consistent signals across common lab workflows.
  • Exceptional Lot-to-Lot Consistency: Tight lot-to-lot control for reproducible performance.
  • Customization Options: Flexible customization of tags, labels, or packaging upon request.

Custom IL6ST Membrane Protein and Antibody Discovery Services

In addition to our catalog products, we also provide custom services for membrane protein and antibody discovery and development. Utilizing our years of experience in cytokine receptor biology and JAK-STAT pathway pharmacology, we can help you with:

  • Custom IL6ST Receptor Production: Tailored expression, purification, and characterization of challenging multi-domain receptor constructs.
  • Custom Antibody Development: From antigen design to antibody engineering (monoclonal, polyclonal, recombinant) for specific research applications.
  • Stable Cell Line Development: Generation of bespoke stable cell lines expressing your target of interest.
  • Functional Assay Development: Designing and executing assays to assess receptor activation and ligand.

Frequently Asked Questions (FAQ)

  1. Is your IL6ST reagents cleared to enumerate cytokine-responsive cell subsets in vitro clinical diagnostic systems and for monitoring inflammatory disease, or stratifying individual patients?

    No, all reagents and services offered are for research use only and not for diagnostic or therapeutic use.

  2. Do you have stable cell lines which co-express IL6ST and IL6RA to model the JAK-STAT signaling of IL-6–dependent internalization dynamics of gp130 in real-time?

    Yes, we have created dual-stable lines that express full-length IL6ST and IL6RA under constitutive expression in independent loci. Surface heterodimer density and IL-6–stimulated STAT3 reporter induction were documented for each batch, creating a well-characterized cellular platform that enables continuous signal transduction study over time using the same cells without involving transient transfection of heterogeneous factors between studies.

  3. Do you provide stable cell lines that simultaneously express IL6ST with OSMR or LIFR for dissecting shared versus distinct signaling outputs across the OSM, LIF, and IL-6 receptor families?

    Yes, we have generated stable lines in which IL6ST is co-expressed constitutively with oncostatin M receptor or leukemia inhibitory factor receptor (LIF-R) and their respective alpha subunits. Ligand-specific STAT3 versus ERK activation profiles qualify the results of each configuration, allowing comparisons of signal specificity without performing multiple sequential transfections.

  4. Are your IL6ST antibodies broadly cross-reactive with respect to mouse and rat orthologs for translational cytokine biology and inflammation model work?

    Yes, the immunogen sits within a well conserved sequence between mammalian species so detection may reliably be shown in cell preparations and tissue lysates of human, mouse and rat with no need for multiple species specific reagent.

Reference
  1. Martínez-Pérez, Carlos, et al. "The signal transducer IL6ST (gp130) as a predictive and prognostic biomarker in breast cancer." Journal of personalized medicine 11.7 (2021): 618. Under Open Access license CC BY 4.0, without modification. https://doi.org/10.3390/jpm11070618
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