Interferon receptor

Available Resources for Interferon Receptors Research

Creative BioMart provides researchers with a variety of carefully designed products to advance interferon receptor-related research. Our broad product portfolio includes recombinant proteins, protein pre-coupled magnetic beads, cell and tissue lysates, and more, giving researchers access to the tools they need to conduct research across a variety of fields.

In addition to our broad product selection, we are committed to providing a wealth of resources on the interferon receptor. Our resources cover important topics such as pathways, protein function, interacting proteins, related articles, and research areas. These valuable resources provide researchers with a reliable reference for understanding the molecular function of these receptors.

Our Featured Products

Cat.#	Product name	Species	Source (Host)	Tag
IFNAR1-3262H	Recombinant Human IFNAR1 protein, His-tagged	Human	E.coli	His
IFNAR2-14078H	Recombinant Human IFNAR2, GST-tagged	Human	E.coli	GST
IFNGR1-612H	Recombinant Human IFNGR1, Fc-His tagged	Human	Human Cell	Fc/His
IFNGR2-14083H	Recombinant Human IFNGR2, GST-tagged	Human	E.coli	GST

About Interferon Receptors

The interferon receptor is a cell surface receptor that plays a crucial role in mediating the cellular responses to interferons (IFNs). It is responsible for recognizing and binding to IFNs, initiating a cascade of intracellular signaling events that lead to the diverse biological effects exerted by these cytokines. The interferon receptor is composed of multiple subunits that vary depending on the type of interferon.

There are three main types of interferon receptors, corresponding to the three major types of interferons:

• Type I Interferon Receptor (IFNAR): The type I interferon receptor is responsible for binding and responding to Type I interferons, which include IFN-alpha and IFN-beta. It is a heterodimeric receptor composed of two subunits: IFNAR1 and IFNAR2. IFNAR1 is constitutively expressed on the cell surface, while IFNAR2 is induced upon interferon stimulation. Both subunits are essential for full receptor functionality.
• Type II Interferon Receptor (IFNGR): The type II interferon receptor recognizes and responds to IFN-gamma, which is the sole representative of Type II interferons. The IFN-gamma receptor, also known as the IFNGR receptor, is a heterodimeric receptor consisting of two subunits: IFNGR1 and IFNGR2. Both subunits are constitutively expressed on most cell types and are required for the binding and signaling of IFN-gamma.
• Type III Interferon Receptor (IFNLR): The type III interferon receptor is specific to Type III interferons, also known as IFN-lambdas (IFN-lambda1, IFN-lambda2, and IFN-lambda3). The IFN-lambda receptor, also referred to as IFNLR or IL-28R, is a complex composed of two subunits: IL-10R2 and IL-28Rα (or IL-10R2 and IL-10R1). This receptor is distinct from the type I and type II interferon receptors and is responsible for binding and signaling of Type III interferons.

Table1. The receptor systems and accessory signaling molecules used by the three IFN types for signal transduction. (de Weerd NA, 2012)

IFN type	Interferons	Receptor	Signaling molecules
Type I	α (13 types), β, δ, ε, κ, τ, ω, ζ	IFNAR1, IFNAR2	JAK1, Tyk2 STAT-1, -2, -3, -4, -5 MAPK, PI3K, Akt, NFκB p53, PRMT1
Type II	γ	IFNGR1, IFNGR2	JAK1, JAK2 STAT-1,-2, -3, -5 MAPK, PI3K, Akt, NFκB
Type III	λ	IFNLR1, IL10RB	JAK1, Tyk2 STAT-1, -2, -3, -4, -5 MAPK, PI3K, Akt

When an interferon binds to its specific receptor, it triggers a series of intracellular signaling events that activate downstream signaling pathways. The activated receptor recruits and activates intracellular kinases, such as Janus kinases (JAKs), which phosphorylate and activate signal transducer and activator of transcription (STAT) proteins. These activated STAT proteins translocate to the nucleus, where they regulate the transcription of interferon-stimulated genes (ISGs), which contribute to the diverse biological effects of interferons.

Fig.1 Representation of the distinct receptor systems employed by type I, type II and type III IFNs for signal transduction. (de Weerd NA, 2012)

Signaling Mechanism of Interferon Receptors

The signaling mechanism of the interferon receptor involves a complex cascade of intracellular events that transduce the binding of interferons to their specific receptor into cellular responses. The following steps outline the general signaling mechanism of the interferon receptor:

1. Binding of Interferon to the Receptor: Interferons, such as Type I (IFN-alpha, IFN-beta), Type II (IFN-gamma), or Type III (IFN-lambda) interferons, bind to their respective receptors on the cell surface. The specific composition of the receptor depends on the type of interferon. For example, the Type I interferon receptor (IFNAR) is a heterodimeric receptor composed of IFNAR1 and IFNAR2 subunits.

2. Receptor Dimerization and Activation: Interferon binding induces conformational changes in the receptor complex, leading to receptor dimerization or oligomerization. This dimerization allows for the activation of the receptor and initiates downstream signaling.

3. Activation of Janus Kinases (JAKs): The activated interferon receptor recruits and activates Janus kinases (JAKs), which are associated with the intracellular domain of the receptor subunits. JAKs are tyrosine kinases that phosphorylate specific tyrosine residues on the receptor and themselves, leading to their activation.

4. Phosphorylation of STAT Proteins: Activated JAKs phosphorylate and activate signal transducer and activator of transcription (STAT) proteins, such as STAT1, STAT2, and STAT3. The specific STAT proteins involved depend on the type of interferon and receptor.

5. Formation of Transcriptional Complexes: Phosphorylated STAT proteins form homo- or heterodimeric complexes and translocate to the nucleus. In some cases, additional proteins, such as interferon regulatory factors (IRFs), may also be involved in the formation of transcriptional complexes. These complexes bind to specific DNA sequences, such as interferon-stimulated response elements (ISREs) or gamma-activated sequences (GAS), in the promoters of interferon-stimulated genes (ISGs).

6. Transcriptional Activation of Interferon-Stimulated Genes (ISGs): The binding of STAT complexes and other transcription factors to ISREs or GAS elements induces the transcriptional activation of ISGs. ISGs encode various proteins that mediate the antiviral, immunomodulatory, and other cellular responses induced by interferons.

7. Downstream Signaling Pathways: In addition to JAK-STAT signaling, interferon receptor activation can also engage other downstream signaling pathways, such as the mitogen-activated protein kinase (MAPK) pathway, phosphoinositide 3-kinase (PI3K)/Akt pathway, and nuclear factor-kappa B (NF-κB) pathway. These pathways can further amplify and modulate the cellular responses to interferons.

The specific signaling events and pathways activated by the interferon receptor can vary depending on the type of interferon, the composition of the receptor complex, and the cell type. The activation of these signaling pathways ultimately leads to the induction of ISGs, which mediate the diverse cellular responses to interferons, including antiviral defenses, immunomodulation, and growth regulation.

Role of Interferon Receptor in Immunomodulation

• Enhancement of Innate Immune Responses: The interferon receptor signaling pathway stimulates the activation and enhancement of innate immune responses. Interferons promote the activity and cytotoxicity of innate immune cells such as natural killer (NK) cells and macrophages. They enhance the recognition and killing of infected or transformed cells by NK cells through the upregulation of activating receptors. Interferons also enhance the phagocytic and microbicidal activities of macrophages, contributing to the clearance of pathogens.
• Activation and Regulation of Adaptive Immune Responses: Interferons play a crucial role in activating and regulating adaptive immune responses. They promote the differentiation and activation of dendritic cells, which are key antigen-presenting cells involved in initiating adaptive immune responses. Interferons enhance the expression of major histocompatibility complex (MHC) molecules on antigen-presenting cells, facilitating efficient antigen presentation to T cells. They also promote the differentiation and cytotoxic activity of CD8+ cytotoxic T lymphocytes (CTLs), aiding in the elimination of infected or malignant cells.
• Modulation of Cytokine Production: The interferon receptor signaling pathway can modulate the production of cytokines, which are important mediators of immune responses. Interferons can induce the expression of pro-inflammatory cytokines, such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and IL-6, contributing to the initiation and amplification of immune responses. They can also induce the expression of anti-inflammatory cytokines, such as interleukin-10 (IL-10), which help in resolving inflammation and maintaining immune homeostasis.
• Immunoregulation in Autoimmune Diseases: Interferons have been implicated in the pathogenesis of autoimmune diseases, and the interferon receptor plays a role in immunomodulation in these conditions. Dysregulated interferon receptor signaling can lead to the activation of autoreactive immune cells and the production of inflammatory cytokines, perpetuating the autoimmune response. Targeting the interferon receptor or downstream signaling pathways has been explored as a therapeutic approach to modulate interferon-mediated immune responses and alleviate autoimmune diseases.
• Immunosuppression and Immune Tolerance: Interferons can also have immunosuppressive effects and contribute to the establishment of immune tolerance. They can inhibit the proliferation and activation of immune cells, such as T cells and B cells, and regulate the balance between effector and regulatory immune cell populations. Interferon receptor signaling can influence the development and function of regulatory T cells (Tregs), which play a critical role in immune tolerance and prevention of excessive immune responses.

Overall, the interferon receptor is involved in immunomodulation by regulating innate and adaptive immune responses, modulating cytokine production, and contributing to immune tolerance. Its signaling pathway influences various aspects of the immune system, ensuring an appropriate immune response against pathogens, regulating inflammation, and maintaining immune homeostasis.

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Related Reference

1. de Weerd NA, Nguyen T. The interferons and their receptors--distribution and regulation. Immunol Cell Biol. 2012;90(5):483-491.