Related Experiment Video
Updated: Oct 17, 2025
10:00
High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes
Published on: March 24, 2015
13.5K
Signaling by the inhibitory receptor CD200R is rewired by type I interferon
Michiel van der Vlist1,2, M Inês Pascoal Ramos1,2, Lucas L van den Hoogen3
1Center for Translational Immunology, Department of Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
Science Signaling
|October 12, 2021
Summary
Type I interferon (IFN) alters CD200 receptor 1 (CD200R) function, shifting it from inhibitory to proinflammatory signaling. This rewiring, driven by cleaved p120-RasGAP, may contribute to inflammation in systemic lupus erythematosus (SLE).
Area of Science:
- Immunology
- Molecular Biology
- Cellular Signaling
Background:
- CD200 receptor 1 (CD200R) normally inhibits Toll-like receptor (TLR)-induced cytokine production.
- This inhibition involves adaptor protein Dok2 and GTPase activating protein (GAP) p120-RasGAP.
- Cleavage of p120-RasGAP under cellular stress impairs CD200R's inhibitory function.
Purpose of the Study:
- To investigate how type I interferon (IFN) affects CD200R signaling.
- To determine the role of cleaved p120-RasGAP in this process.
- To explore the implications for systemic lupus erythematosus (SLE) pathogenesis.
Main Methods:
- Treatment of human peripheral blood mononuclear cells (PBMC) with interferon-α (IFN-α).
- Analysis of p120-RasGAP cleavage and its effect on CD200R signaling.
- Assessment of TLR-induced IFN-γ expression.
- Comparison of PBMC from SLE patients and healthy controls.
Main Results:
- IFN-α treatment increased cleaved p120-RasGAP and reduced CD200R's inhibition of mTORC1 signaling.
- IFN-α pretreatment switched CD200R from inhibiting to potentiating TLR-induced IFN-γ expression.
- SLE patients showed increased cleaved p120-RasGAP and altered CD200R function.
Conclusions:
- Type I IFN signaling rewires CD200R to promote inflammation.
- Cleaved p120-RasGAP is a key mediator of this switch.
- Dysregulated CD200R signaling may contribute to SLE pathogenesis.
Related Concept Videos
01:19Interactions Between Signaling Pathways
6.7K
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...
6.7K
01:24Intracellular Signaling Cascades
48.8K
Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
48.8K
01:22Amplifying Signals via Enzymatic Cascade
13.7K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
13.7K
01:15Receptor Downregulation in MVBs
2.3K
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...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.3K
01:20The JAK-STAT Signaling Pathway
9.6K
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...
9.6K
01:16TGF - β Signaling Pathway
8.0K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
8.0K