GO:0032003 interleukin-28 receptor binding: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0032003 (interleukin-28 receptor binding) is a molecular function defined as binding to an interleukin-28 receptor [QuickGO].
• The interleukin-28 receptor is a heterodimeric complex of IL28RA (also known as IFNLR1) and IL10RB, which mediates signaling by type III interferons including IL-28A, IL-28B, and IL-29.
• Interleukin-28 receptor binding triggers JAK1/STAT1 phosphorylation and downstream antiviral and immunomodulatory gene expression.
• Dysregulation of this binding is implicated in acute myocardial infarction through phosphorylated JAK1/STAT1 signaling pathways.
• Interferon-induced depression has been associated with glucocorticoid receptors, BDNF, serotonin, and dopamine neurotransmission, which may intersect with interleukin-28 receptor signaling.
• Personalized medicine approaches in Alzheimer's disease and depression may benefit from understanding interleukin-28 receptor binding and its downstream effects.
Description
Interleukin-28 receptor binding (GO:0032003) is a molecular function that describes the binding of a ligand to an interleukin-28 receptor. This term is part of the Gene Ontology molecular function aspect and is critical for understanding how type III interferons, such as IL-28A, IL-28B, and IL-29, initiate signaling cascades. The interleukin-28 receptor is a heterodimeric complex composed of IL28RA (IFNLR1) and IL10RB, and its activation leads to JAK1/STAT1 phosphorylation, which drives antiviral and immunomodulatory responses. Researchers study this term to dissect the initial steps of cytokine-receptor interactions and their roles in health and disease. The binding event is a key checkpoint in interferon signaling, and its dysregulation has been linked to conditions such as acute myocardial infarction and interferon-induced depression. Understanding the molecular details of interleukin-28 receptor binding can inform therapeutic strategies targeting this pathway.
interleukin-28 receptor binding At A Glance
| GO ID | GO:0032003 |
|---|---|
| GO term | interleukin-28 receptor binding |
| Ontology | molecular_function |
| Synonym | IL-28, interleukin-28 receptor ligand |
| Definition | Binding to an interleukin-28 receptor. |
| Major function | Mediates ligand-receptor interaction for type III interferon signaling |
| Receptor complex | Heterodimer of IL28RA (IFNLR1) and IL10RB |
| Downstream signaling | JAK1/STAT1 phosphorylation pathway |
What Is GO:0032003?
According to the Gene Ontology, GO:0032003 (interleukin-28 receptor binding) is defined as the binding to an interleukin-28 receptor. This molecular function encompasses the interaction between a ligand, such as interleukin-28 (IL-28), and its specific receptor, the interleukin-28 receptor. The term is synonymous with IL-28 and interleukin-28 receptor ligand. It represents an early event in receptor activation and is essential for transmitting signals from the extracellular environment to the intracellular signaling machinery.
Why Is interleukin-28 receptor binding Important in Cell Biology?
Interleukin-28 receptor binding is a critical molecular event that initiates type III interferon signaling, which plays a central role in antiviral defense and immune regulation. Dysregulation of this binding and its downstream JAK1/STAT1 pathway has been implicated in acute myocardial infarction, where inhibition of IL28RA showed potential therapeutic effects. Additionally, interferon-induced depression has been associated with alterations in glucocorticoid receptors, BDNF, serotonin, and dopamine neurotransmission, suggesting that interleukin-28 receptor binding may contribute to neuropsychiatric symptoms. Understanding this binding event is therefore important for developing targeted therapies for cardiovascular, infectious, and neuropsychiatric diseases.
• Initiates antiviral responses through type III interferon signaling.
• Activates JAK1/STAT1 phosphorylation, a key signaling axis in immune cells.
• Modulates immune cell function and cytokine production.
• Implicated in acute myocardial infarction pathogenesis.
• May contribute to interferon-induced depression via neuroimmune interactions.
• Potential target for personalized medicine in Alzheimer's disease and depression.
• Provides a model for studying cytokine-receptor binding specificity.
• Relevant for understanding host-pathogen interactions and viral evasion.
• Can be explored for therapeutic modulation of interferon responses.
• Bridges molecular function to disease phenotypes in cardiovascular and neuropsychiatric disorders.
What Happens During interleukin-28 receptor binding?
Ligand Recognition and Binding
In simple terms: The ligand, such as IL-28, finds and attaches to its specific receptor on the cell surface.
Interleukin-28 receptor binding begins with the recognition of the interleukin-28 receptor by its ligand, which can be IL-28A, IL-28B, or IL-29. The receptor is a heterodimer of IL28RA (IFNLR1) and IL10RB. Binding is highly specific and initiates a conformational change in the receptor complex. This event is the first step in a signaling cascade that leads to antiviral and immunomodulatory effects.
Receptor Activation and JAK1/STAT1 Phosphorylation
In simple terms: Once the ligand binds, the receptor activates enzymes called JAK1, which then phosphorylate STAT1 to transmit the signal.
Upon ligand binding, the interleukin-28 receptor-associated JAK1 kinases are activated and phosphorylate STAT1. This phosphorylation event is a hallmark of interleukin-28 receptor signaling and has been demonstrated in the context of acute myocardial infarction, where inhibition of IL28RA modulated phosphorylated JAK1/STAT1 pathways. The phosphorylated STAT1 then translocates to the nucleus to regulate gene expression.
Downstream Gene Expression and Antiviral Activity
In simple terms: The signal reaches the nucleus and turns on genes that fight viruses and regulate the immune system.
Phosphorylated STAT1 dimers bind to DNA and induce the expression of interferon-stimulated genes (ISGs), which confer antiviral activity. In virus-infected human myeloid dendritic cells, interleukin-29 (a ligand for the interleukin-28 receptor) induced gene expression and antiviral activity. This downstream response is critical for controlling viral infections and shaping adaptive immunity.
Regulation and Crosstalk with Other Pathways
In simple terms: The binding and its effects can be influenced by other signals in the cell, such as stress hormones and neurotransmitters.
Interleukin-28 receptor binding and its downstream signaling can be modulated by other pathways. For instance, interferon-induced depression has been associated with glucocorticoid receptors, BDNF, serotonin, and dopamine neurotransmission, suggesting crosstalk between interferon signaling and neuroendocrine systems. This regulation may affect the intensity and duration of the response to interleukin-28 receptor binding.
Key Genes Involved in GO:0032003 interleukin-28 receptor binding
The following genes and proteins are directly involved in interleukin-28 receptor binding and its downstream signaling.
| Gene | Major Role | Research Relevance |
|---|---|---|
| IL28RA (IFNLR1) | Alpha subunit of the interleukin-28 receptor; binds IL-28 and IL-29 | Target for inhibition in acute myocardial infarction |
| IL10RB | Beta subunit of the interleukin-28 receptor; required for signaling | Essential for receptor complex formation and signaling |
| IL28A (IFNL2) | Ligand for interleukin-28 receptor | Induces antiviral responses |
| IL28B (IFNL3) | Ligand for interleukin-28 receptor | Associated with interferon-based therapies |
| IL29 (IFNL1) | Ligand for interleukin-28 receptor | Shown to induce gene expression in dendritic cells |
| JAK1 | Kinase that phosphorylates STAT1 upon receptor activation | Mediates downstream signaling |
| STAT1 | Transcription factor activated by JAK1; regulates ISGs | Key effector of interleukin-28 receptor signaling |
| STAT2 | Part of ISGF3 complex with STAT1 | Contributes to interferon-stimulated gene expression |
| IRF9 | Part of ISGF3 complex | Mediates transcriptional activation |
| SOCS1 | Negative regulator of JAK/STAT signaling | Feedback inhibition of interleukin-28 receptor signaling |
| SOCS3 | Negative regulator of JAK/STAT signaling | Modulates interferon responses |
| PTPN11 (SHP2) | Phosphatase that can regulate JAK/STAT | Potential modulator of signaling |
| BDNF | Neurotrophic factor linked to interferon-induced depression | Associated with depression |
| SLC6A4 (SERT) | Serotonin transporter | Linked to interferon-induced depression |
| DRD2 | Dopamine receptor D2 | Linked to interferon-induced depression |
| NR3C1 (GR) | Glucocorticoid receptor | Associated with interferon-induced depression |
| APOE | Lipoprotein involved in Alzheimer's disease | Relevant to personalized medicine |
How Is interleukin-28 receptor binding Regulated?
Interleukin-28 receptor binding and its downstream signaling are regulated at multiple levels. Negative feedback loops involving SOCS proteins can attenuate JAK/STAT signaling. Additionally, crosstalk with neuroendocrine pathways, such as glucocorticoid receptor signaling, BDNF, serotonin, and dopamine neurotransmission, has been implicated in interferon-induced depression. Personalized medicine approaches in Alzheimer's disease and depression may consider genetic variants affecting these regulatory networks.
interleukin-28 receptor binding and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| IL28RA (IFNLR1) | Acute myocardial infarction | Knockout or point-mutation cell models |
| IL28B (IFNL3) | Viral infection and interferon response | Overexpression and knockout models |
| BDNF | Interferon-induced depression | Knockout and knock-in models |
| SLC6A4 (SERT) | Interferon-induced depression | Point-mutation models |
| APOE | Alzheimer's disease | Knock-in models |
Acute Myocardial Infarction
Inhibition of IL28RA, the alpha subunit of the interleukin-28 receptor, has shown potential therapeutic effects on acute myocardial infarction through modulation of phosphorylated JAK1/STAT1 signaling pathways. This suggests that interleukin-28 receptor binding and its downstream signaling contribute to cardiac injury and could be targeted for cardioprotection.
Interferon-Induced Depression
Interferon-induced depression has been associated with glucocorticoid receptors, brain-derived neurotrophic factor (BDNF), serotonin, and dopamine neurotransmission. Since interleukin-28 receptor binding initiates interferon signaling, it may play a role in the neuropsychiatric side effects of interferon therapy. Understanding this link could inform strategies to manage depression in patients receiving interferon-based treatments.
Alzheimer's Disease and Personalized Medicine
Personalized medicine approaches in Alzheimer's disease and depression may benefit from understanding interleukin-28 receptor binding and its genetic determinants. Variations in genes involved in this pathway could influence disease susceptibility and treatment response, highlighting the need for further research.
From interleukin-28 receptor binding-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does IL28RA knockout affect JAK1/STAT1 signaling? | IL28RA knockout cell line |
| What is the effect of IL28RA point mutations on ligand binding? | Point-mutation knock-in cell models |
| Can overexpression of IL28 ligands enhance antiviral responses? | Overexpression cell models |
| How does IL10RB contribute to receptor complex formation? | IL10RB knockout and tagged knock-in models |
| What is the role of STAT1 phosphorylation in myocardial infarction? | STAT1 knockout and phospho-mutant models |
| Does BDNF modulation affect interferon-induced depression? | BDNF knockout and overexpression models |
How to Study the interleukin-28 receptor binding Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Surface plasmon resonance (SPR) | Binding affinity and kinetics | Ligand-receptor interaction studies |
| Western blotting | Phosphorylation of JAK1 and STAT1 | Signaling pathway activation |
| RNA-seq | Gene expression changes | Interferon-stimulated gene profiling |
| Immunoprecipitation | Protein-protein interactions | Receptor complex assembly |
| Luciferase reporter assay | Transcriptional activity of STAT1 | Functional validation of signaling |
| ELISA | Cytokine levels | Immune response quantification |
| Behavioral tests | Depression-like phenotypes | Interferon-induced depression models |
| Genotyping | Genetic variants in IL28RA/IL28B | Personalized medicine studies |
Binding Assays
Surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) can measure the binding affinity between interleukin-28 ligands and the interleukin-28 receptor. These methods provide kinetic and thermodynamic parameters essential for understanding the molecular function.
Phosphorylation Analysis
Western blotting and immunoprecipitation can detect phosphorylated JAK1 and STAT1 following interleukin-28 receptor binding. This approach has been used to demonstrate the involvement of phosphorylated JAK1/STAT1 in acute myocardial infarction.
Gene Expression Profiling
RNA-seq and quantitative PCR can measure interferon-stimulated gene expression after receptor activation. In virus-infected human myeloid dendritic cells, interleukin-29 induced gene expression and antiviral activity.
Neuropsychiatric Assessments
In clinical and preclinical studies, depression-like behaviors and neurotransmitter levels can be assessed to evaluate the impact of interferon signaling on the brain. Glucocorticoid receptors, BDNF, serotonin, and dopamine neurotransmission have been associated with interferon-induced depression.
How CRISPR Can Be Used to Study GO:0032003 interleukin-28 receptor binding
Knockout
CRISPR knockout of IL28RA or IL10RB can abolish interleukin-28 receptor binding and downstream signaling, providing a clean model to study the loss of function. Such models are useful for validating the role of this pathway in acute myocardial infarction and antiviral responses.
Point Mutation
Introducing point mutations in the ligand-binding domain of IL28RA or in the ligand itself can dissect the specific residues required for interleukin-28 receptor binding. These models help distinguish binding affinity from downstream signaling efficacy.
Knock-in
Knock-in of tagged receptors (e.g., HA-tagged IL28RA) allows for visualization and pull-down of the receptor complex. This approach can be used to study receptor trafficking and interaction partners in the context of interleukin-28 receptor binding.
Overexpression
Overexpression of IL28 ligands or the receptor subunits can amplify signaling and enhance antiviral responses. This is particularly useful for studying gene expression changes and antiviral activity in cell models.
How EDITGENE Supports interleukin-28 receptor binding Research
Researchers studying interleukin-28 receptor binding-related genes often need to determine whether a candidate gene is causally involved in the pathway or merely correlated with a phenotype. EDITGENE provides a comprehensive suite of CRISPR-based services to enable precise genetic manipulation and functional validation.
Contact EDITGENE today to design your custom CRISPR model for interleukin-28 receptor binding research.
Frequently Asked Questions About interleukin-28 receptor binding
What is interleukin-28 receptor binding?
Interleukin-28 receptor binding (GO:0032003) is a molecular function defined as the binding to an interleukin-28 receptor, initiating type III interferon signaling.
What genes are involved in interleukin-28 receptor binding?
Key genes include IL28RA (IFNLR1), IL10RB, IL28A, IL28B, IL29, JAK1, and STAT1.
What is the GO ID for interleukin-28 receptor binding?
The GO ID is GO:0032003.
How does interleukin-28 receptor binding affect the immune system?
It triggers JAK1/STAT1 phosphorylation and induces interferon-stimulated genes, enhancing antiviral and immunomodulatory responses.
Is interleukin-28 receptor binding involved in disease?
Yes, it has been implicated in acute myocardial infarction and interferon-induced depression.
What are the synonyms for interleukin-28 receptor binding?
Synonyms include IL-28 and interleukin-28 receptor ligand.
What research methods are used to study interleukin-28 receptor binding?
Methods include surface plasmon resonance, Western blotting, RNA-seq, and CRISPR knockout models.
Can CRISPR be used to study interleukin-28 receptor binding?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models are valuable for dissecting this pathway.
What is the role of IL28RA in myocardial infarction?
Inhibition of IL28RA has shown potential therapeutic effects on acute myocardial infarction through phosphorylated JAK1/STAT1 signaling pathways.
How is interleukin-28 receptor binding related to depression?
Interferon-induced depression has been associated with glucocorticoid receptors, BDNF, serotonin, and dopamine neurotransmission, which may intersect with interleukin-28 receptor signaling.
Conclusion
Interleukin-28 receptor binding (GO:0032003) is a fundamental molecular function that initiates type III interferon signaling, with critical roles in antiviral defense and immune regulation. Its dysregulation is linked to acute myocardial infarction and interferon-induced depression, making it a target of therapeutic interest. Advances in CRISPR-based models and bioinformatics will continue to elucidate the precise mechanisms and disease relevance of this binding event, supporting personalized medicine approaches.
References
- 1. Souslova T et al.. 2013. Personalized medicine in Alzheimer's disease and depression.. Contemp Clin Trials 36(2):616-23 PMID: 23816492
- 2. Gong G et al.. 2024. Potential therapeutic effects of IL28RA inhibition on acute myocardial infarction through phosphorylated JAK1/STAT1 signaling pathways.. Sci Rep 14(1):30576 PMID: 39706854
- 3. Udina M et al.. 2016. Glucocorticoid Receptors, Brain-Derived Neurotrophic Factor, Serotonin and Dopamine Neurotransmission are Associated with Interferon-Induced Depression.. Int J Neuropsychopharmacol 19(4) PMID: 26721949
- 4. Osterlund P et al.. 2005. Gene expression and antiviral activity of alpha/beta interferons and interleukin-29 in virus-infected human myeloid dendritic cells.. J Virol 79(15):9608-17 PMID: 16014923
