ArticleThe Journal of biological chemistry2014
The amino acid exchange R28E in ciliary neurotrophic factor (CNTF) abrogates interleukin-6 receptor-dependent but retains CNTF receptor-dependent signaling via glycoprotein 130 (gp130)/leukemia inhibitory factor receptor (LIFR).
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- Research progress on S-palmitoylation modification mediated by the ZDHHC family in glioblastoma.Frontiers in cell and developmental biology · 2024Review
- Cytokimera GIL-11 rescued IL-6R deficient mice from partial hepatectomy-induced death by signaling via non-natural gp130:LIFR:IL-11R complexes.Communications biology · 2023Article
- Modulation of matrix metalloproteases by ciliary neurotrophic factor in human placental development.Cell and tissue research · 2022Article
- Ciliary neurotrophic factor (CNTF) and its receptor (CNTFRα) signal through MAPK/ERK pathway in human prostate tissues: a morphological and biomolecular study.European journal of histochemistry : EJH · 2020Article
- Characterization, Stability, and in Vivo Efficacy Studies of Recombinant Human CNTF and Its Permeation into the Neural Retina in ex Vivo Organotypic Retinal Explant Culture Models.Pharmaceutics · 2020Article
- Engineering a potent receptor superagonist or antagonist from a novel IL-6 family cytokine ligand.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- microRNA-146a Promotes Growth of Acute Leukemia Cells by Downregulating Ciliary Neurotrophic Factor Receptor and Activating JAK2/STAT3 Signaling.Yonsei medical journal · 2019Article
- Effects of leukemia inhibitory factor receptor on the adipogenic differentiation of human bone marrow mesenchymal stem cells.Molecular medicine reports · 2019Article
- miR-377-3p regulates adipogenic differentiation of human bone marrow mesenchymal stem cells by regulating LIFR.Molecular and cellular biochemistry · 2018Article
- Therapeutic effect of transmembrane TAT-tCNTF via Erk and Akt activation usingInternational journal of clinical and experimental pathology · 2018Article
- [Expression of miR-140-5p and prediction of its target gene in human mesenchymal stem cells during adipogenic differentiation].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2016Article
- Ciliary neurotrophic factor has intrinsic and extrinsic roles in regulating B cell differentiation and bone structure.Scientific reports · 2015Article
- Codon optimization and factorial screening for enhanced soluble expression of human ciliary neurotrophic factor in Escherichia coli.BMC biotechnology · 2014Article
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11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ciliary neurotrophic factor (CNTF) is a neurotrophic factor with therapeutic potential for neurodegenerative diseases. Moreover, therapeutic application of CNTF reduced body weight in mice and humans. CNTF binds to high or low affinity receptor complexes consisting of CNTFR·gp130·LIFR or IL-6R·gp130·LIFR, respectively. Clinical studies of the CNTF derivative Axokine revealed intolerance at higher concentrations, which may rely on the low-affinity binding of CNTF to the IL-6R. Here, we aimed to generate a CNTFR-selective CNTF variant (CV). CV-1 contained the single amino acid exchange R28E. Arg(28) is in close proximity to the CNTFR binding site. Using molecular modeling, we hypothesized that Arg(28) might contribute to IL-6R/CNTFR plasticity of CNTF. CV-2 to CV-5 were generated by transferring parts of the CNTFR-binding site from cardiotrophin-like cytokine to CNTF. Cardiotrophin-like cytokine selectively signals via the CNTFR·gp130·LIFR complex, albeit with a much lower affinity compared with CNTF. As shown by immunoprecipitation, all CNTF variants retained the ability to bind to CNTFR. CV-1, CV-2, and CV-5, however, lost the ability to bind to IL-6R. Although all variants induced cytokine-dependent cellular proliferation and STAT3 phosphorylation via CNTFR·gp130·LIFR, only CV-3 induced STAT3 phosphorylation via IL-6R·gp130·LIFR. Quantification of CNTF-dependent proliferation of CNTFR·gp130·LIFR expressing cells indicated that only CV-1 was as biologically active as CNTF. Thus, the CNTFR-selective CV-1 will allow discriminating between CNTFR- and IL-6R-mediated effects in vivo.
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