ArticleThe Biochemical journal2007
Comparable potency of IFNalpha2 and IFNbeta on immediate JAK/STAT activation but differential down-regulation of IFNAR2.
Article in The Biochemical journal, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
49 citing papers in PubMed, 76 citations in OpenAlex.
- Integrating in vitro aerosol characterization and cross-species PBPK modeling to predict human lung exposure of inhaled therapeutic proteins.International journal of pharmaceutics: X · 2026Article
- Mechanisms of Differential Signal Transduction by Interferon Lambda Receptor 1 Variants.Journal of innate immunity · 2026Article
- Interferon-Based Therapeutics in Cancer Therapy: Past, Present, and Future.International journal of molecular sciences · 2025Review
- Type I IFNs enhance human dorsal root ganglion nociceptor excitability and induce TRPV1 sensitization.JCI insight · 2025Article
- Mechanisms of Differential Signal Transduction by IFNLR1 Variants.bioRxiv : the preprint server for biology · 2025Article
- Cloning and Functional Characterization of Novel Human Neutralizing Anti-IFN-α and Anti-IFN-β Antibodies.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Molecular and cellular factors determining the functional pleiotropy of cytokines.The FEBS journal · 2023Review
- STAM and Hrs interact sequentially with IFN-α Receptor to control spatiotemporal JAK-STAT endosomal activation.Nature cell biology · 2023Article
- Anti-IFN-α/-ω neutralizing antibodies from COVID-19 patients correlate with downregulation of IFN response and laboratory biomarkers of disease severity.European journal of immunology · 2022Article
- The Landscape of IFN/ISG Signaling in HIV-1-Infected Macrophages and Its Possible Role in the HIV-1 Latency.Cells · 2021Review
- Determinants of Ligand Specificity and Functional Plasticity in Type I Interferon Signaling.Frontiers in immunology · 2021Article
- HIV infection does not alter interferon α/β receptor 2 expression on mucosal immune cells.PloS one · 2020Article
- Interferon Receptor Trafficking and Signaling: Journey to the Cross Roads.Frontiers in immunology · 2020Review
- Shared and Unique Features of Human Interferon-Beta and Interferon-Alpha Subtypes.Frontiers in immunology · 2020Review
- Context Is Key: Delineating the Unique Functions of IFNα and IFNβ in Disease.Frontiers in immunology · 2020Review
- MALAT1 is involved in type I IFNs-mediated systemic lupus erythematosus by up-regulating OAS2, OAS3, and OASL.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2020Article
- Autoreactive B cells in SLE, villains or innocent bystanders?Immunological reviews · 2019Review
- Hypersensitive IFN Responses in Lupus Keratinocytes Reveal Key Mechanistic Determinants in Cutaneous Lupus.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Differential Regulation of Type I and Type III Interferon Signaling.International journal of molecular sciences · 2019Review
- CCR2 Signaling Selectively Regulates IFN-α: Role of β-Arrestin 2 in IFNAR1 Internalization.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type I IFNs (interferons) (IFNalpha/beta) form a family of related cytokines that control a variety of cellular functions through binding to a receptor composed of IFNAR (IFNalpha receptor subunit) 1 and 2. Among type I IFNs, the alpha2 and beta subtypes exhibit a large difference in their binding affinities to IFNAR1, and it was suggested that high concentrations of IFNAR1 may compensate for its low intrinsic binding affinity for IFNalpha2. We tested whether receptor-proximal signalling events are sensitive to IFNAR1 surface concentration by investigating the relationship between relative IFNAR1/IFNAR2 surface levels and IFNalpha2 and IFNbeta signalling potencies in several cell lines. For this, we monitored the activation profile of JAK (Janus kinase)/STAT (signal transducer and activator of transcription) proteins, measured basal and ligand-induced surface decay of each receptor subunit and tested the effect of variable IFNAR1 levels on IFNalpha2 signalling potency. Our data show that the cell-surface IFNAR1 level is indeed a limiting factor for assembly of the functional complex, but an increased concentration of it does not translate into an IFNalpha/beta differential JAK/STAT signalling nor does it change the dynamics of the engaged receptor. Importantly, however, our data highlight a differential effect upon routing of IFNAR2. Following binding of IFNalpha2, IFNAR2 is internalized, but, instead of being routed towards degradation as it is when complexed to IFNbeta, it recycles back to the cell surface. These observations suggest strongly that the stability and the intracellular lifetime of the ternary complex account for the differential control of IFNAR2. Moreover, the present study opens up the attractive possibility that endosomal-initiated signalling may contribute to IFNalpha/beta differential bioactivities.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.