Related Experiment Video
Updated: May 31, 2026
08:40
An ELISA Based Binding and Competition Method to Rapidly Determine Ligand-receptor Interactions
Published on: March 14, 2016
Mechanisms of Differential Signal Transduction by Interferon Lambda Receptor 1 Variants
Laura A Novotny1, Carla Martinez-Morant2, Stephen A Duncan2
1Division of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.
Journal of Innate Immunity
|May 29, 2026
Summary
Different interferon lambda receptor-1 (IFNLR1) variants signal differently, affecting interferon-stimulated gene (ISG) induction. This suggests IFNLR1 variants play a role in regulating cellular responses to interferons.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Lambda interferons (IFNLs) signal via the interferon lambda receptor-1 (IFNLR1) and IL10RB receptor complex to induce interferon-stimulated genes (ISGs).
- Distinct IFNLR1 splice variants influence gene expression and HBV replication in hepatocytes.
- This study investigates the signal transduction mechanisms of full-length IFNLR1 (variant 1) and a truncated variant (variant 2).
Purpose of the Study:
- To compare the signal transduction mechanisms of two IFNLR1 variants (full-length and truncated).
- To evaluate how these variants affect IFNL-induced signaling pathways and gene expression in hepatocytes.
Main Methods:
- Utilized HEK293T cells, wild-type (WT), and IFNLR1 knock-out (KO) hepatocytes with inducible IFNLR1 variant expression.
- Employed Duolink proximity ligation assay, ImageStream flow cytometry, western blotting, and gene expression profiling.
- Assessed susceptibility to JAK1 and TYK2 inhibitors to determine signaling pathway dependence.
Main Results:
- Both IFNLR1 variants localized with IL10RB, but variant 1 showed faster internalization.
- Overexpression of either variant in WT hepatocytes enhanced IFNL-induced phosphorylation of JAK1, TYK2, STAT1, and STAT2.
- Variant 2 exhibited reduced ISG induction and JAK1/TYK2 phosphorylation in KO hepatocytes compared to variant 1, despite comparable STAT1/STAT2 phosphorylation.
Conclusions:
- IFNLR1 variants differentially utilize signaling mediators to modulate IFNL-induced gene expression.
- These findings suggest a regulatory role for IFNLR1 variants in interferon signaling pathways.
Related Concept Videos
01:26Signal Transduction: Overview
Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
Typically, signal transduction involves three...
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
01:41Non-Canonical Wnt Signaling Pathways
Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
02:26NF-κB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
01:19Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...