ArticleJournal of virology2009
Unraveling viral interleukin-6 binding to gp130 and activation of STAT-signaling pathways independently of the interleukin-6 receptor.
Article in Journal of virology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
33 citing papers in PubMed, 57 citations in OpenAlex.
- Interleukin-11 receptor is an alternative α-receptor for interleukin-6 and the chimeric cytokine IC7.The FEBS journal · 2025Article
- Engineering synthetic signaling receptors to enable erythropoietin-free erythropoiesis.Nature communications · 2025Article
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- 5-AZA Upregulates SOCS3 and PTPN6/SHP1, Inhibiting STAT3 and Potentiating the Effects of AG490 against Primary Effusion Lymphoma Cells.Current issues in molecular biology · 2024Article
- Autoimmune hypoglycemia expands the biological spectrum of HHV8+ multicentric Castleman disease.Blood advances · 2021Article
- Interleukin 35 Regulatory B Cells.Journal of molecular biology · 2021Review
- An Immunocompetent HIV-Negative Elderly Patient with Low-Grade Fever, Generalized Lymphadenopathy, Splenomegaly, and Acute Phase Response: Do Not Forget Castleman Disease.Case reports in infectious diseases · 2021Article
- The role of IL-6 and other mediators in the cytokine storm associated with SARS-CoV-2 infection.The Journal of allergy and clinical immunology · 2020Review
- Expression of phosphorylated estrogen receptor beta is an independent negative prognostic factor for pancreatic ductal adenocarcinoma.Journal of cancer research and clinical oncology · 2018Article
- TLR4-Mediated Inflammation Promotes KSHV-Induced Cellular Transformation and Tumorigenesis by Activating the STAT3 Pathway.Cancer research · 2017Article
- The role of IL-6 in host defence against infections: immunobiology and clinical implications.Nature reviews. Rheumatology · 2017Review
- Interleukin 35: Critical regulator of immunity and lymphocyte-mediated diseases.Cytokine & growth factor reviews · 2015Review
- Castleman Disease.Federal practitioner : for the health care professionals of the VA, DoD, and PHS · 2015Article
- Article
- Interleukin 35-Producing B Cells (i35-Breg): A New Mediator of Regulatory B-Cell Functions in CNS Autoimmune Diseases.Critical reviews in immunology · 2015Review
- Human herpesvirus 8 viral interleukin-6 signaling through gp130 promotes virus replication in primary effusion lymphoma and endothelial cells.Journal of virology · 2014Article
- 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).The Journal of biological chemistry · 2014Article
- Herbal extract SH003 suppresses tumor growth and metastasis of MDA-MB-231 breast cancer cells by inhibiting STAT3-IL-6 signaling.Mediators of inflammation · 2014Article
- Human herpesvirus 8 interleukin-6 contributes to primary effusion lymphoma cell viability via suppression of proapoptotic cathepsin D, a cointeraction partner of vitamin K epoxide reductase complex subunit 1 variant 2.Journal of virology · 2014Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human herpesvirus 8 encodes a viral version of interleukin-6 (vIL-6) which shows 25% sequence homology with human IL-6. In contrast to human IL-6, which first binds to the IL-6 receptor (IL-6R) and only subsequently associates with the signal transducing receptor subunit gp130, vIL-6 has been shown to directly bind to gp130 without the need of IL-6R. As a functional consequence, vIL-6 can activate far more target cells in the body since all cells express gp130, but only cells such as hepatocytes and some leukocytes express IL-6R. We sought to understand which amino acid sequences within the vIL-6 protein were responsible for its ability to bind and activate gp130 independent of IL-6R. As a first approach, we constructed chimeric IL-6 proteins in which all known gp130 interacting sites (sites II and III) were sequentially transferred from vIL-6 into the human IL-6 protein. To our surprise, human IL-6 carrying all gp130 interacting sites from vIL-6 did not show IL-6R-independent gp130 activation. Even more surprisingly, the loop between helix B and C of vIL-6, clearly shown in the crystal structure not to be in contact with gp130, is indispensable for direct binding to and activation of gp130. This points to an IL-6R induced change of site III conformation in human IL-6, which is already preformed in vIL-6. These data indicate a novel activation mechanism of human IL-6 by the IL-6R that will be important for the construction of novel hyperactive cytokine variants.
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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.