Related Experiment Video

Updated: May 17, 2026

Adoptive Immunotherapy of iNKT Cells in Glucose-6-Phosphate Isomerase (G6PI)-Induced RA Mice
08:43

Adoptive Immunotherapy of iNKT Cells in Glucose-6-Phosphate Isomerase (G6PI)-Induced RA Mice

Published on: January 31, 2020

Type I IFN receptor controls activated TYK2 in the nucleus: implications for EAE therapy

Chulbul M Ahmed1, Ezra N Noon-Song, Kaisa Kemppainen

  • 1Department of Microbiology and Cell Science, University of Florida, Gainesville, FL 32611, United States. ahmed1@ufl.edu

Journal of Neuroimmunology
|November 1, 2012
PubMed

Insights

Type I interferon signaling involves Janus kinase TYK2 in the nucleus, impacting OAS1 gene epigenetics. This discovery may lead to new therapeutics for viral infections and multiple sclerosis.

Area of Science:

  • Immunology
  • Molecular Biology
  • Epigenetics

Background:

  • Janus kinase 2 (JAK2) is implicated in histone modification and epigenetics.
  • Type I interferon (IFN) signaling pathways are crucial for immune responses.

Purpose of the Study:

  • To investigate the role of Tyrosine Kinase 2 (TYK2) in Type I IFN signaling within the nucleus.
  • To explore the epigenetic modifications at the OAS1 gene promoter during IFN treatment.
  • To evaluate the therapeutic potential of novel IFN mimetics.

Main Methods:

  • Chromatin immunoprecipitation followed by PCR (ChIP-PCR) to detect protein and histone modifications at the OAS1 promoter.
  • Immunoprecipitation to identify nuclear protein complexes.
  • Western blotting and confocal microscopy to confirm protein localization and activation.
  • Assessment of antiviral and anti-inflammatory properties of truncated IFN mimetics.

Main Results:

  • Activated TYK2 was found in the nucleus during Type I IFN signaling.
  • IFNAR1, IFNAR2, TYK2, STAT1, and H3pY41 were localized to the OAS1 gene promoter in IFN-treated cells.
  • A complex of IFNAR1, TYK2, and STAT1α was identified in the nucleus.
  • IFN treatment induced demethylation and subsequent acetylation of histone H3 lysine 9 at the OAS1 promoter.
  • Truncated IFN mimetics demonstrated intracellular antiviral activity and therapeutic effects in experimental allergic encephalomyelitis without significant side effects.

Conclusions:

  • Type I IFN signaling is a complex process involving nuclear TYK2 and epigenetic modifications at specific gene promoters.
  • Nuclear localization and activation of TYK2 are critical for IFN-mediated gene regulation.
  • Epigenetic changes, including histone modifications at the OAS1 promoter, are key events in IFN response.
  • Novel IFN mimetics hold promise as therapeutics for viral diseases and multiple sclerosis.

More Related Videos

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes09:40

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes

Published on: September 28, 2018

Vasodilation of Isolated Vessels and the Isolation of the Extracellular Matrix of Tight-skin Mice08:09

Vasodilation of Isolated Vessels and the Isolation of the Extracellular Matrix of Tight-skin Mice

Published on: March 24, 2017

Related Concept Videos

Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
NF-κB-dependent Signaling Pathway02:26

NF-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...
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...