ArticleMolecular biology of the cell2006
Forced dimerization of gp130 leads to constitutive STAT3 activation, cytokine-independent growth, and blockade of differentiation of embryonic stem cells.
Article in Molecular biology of the cell, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 72 citations in OpenAlex.
- GP130 activation induces myeloma and collaborates with MYC.The Journal of clinical investigation · 2014Trial
- A single amino acid in the Salmonella effector SarA/SteE triggers supraphysiological activation of STAT3 for anti-inflammatory gene expression.Cell reports · 2025Article
- Cell-autonomous IL6ST activation suppresses prostate cancer development via STAT3/ARF/p53-driven senescence and confers an immune-active tumor microenvironment.Molecular cancer · 2024Article
- Modular chimeric cytokine receptors with leucine zippers enhance the antitumour activity of CAR T cells via JAK/STAT signalling.Nature biomedical engineering · 2024Article
- Targeting IL-6 trans-signalling: past, present and future prospects.Nature reviews. Immunology · 2023Review
- Molecular and cellular factors determining the functional pleiotropy of cytokines.The FEBS journal · 2023Review
- Regulatory role of short-chain fatty acids in inflammatory bowel disease.Cell communication and signaling : CCS · 2022Review
- The two facets of gp130 signalling in liver tumorigenesis.Seminars in immunopathology · 2021Review
- Article
- Endosomes as Signaling Platforms for IL-6 Family Cytokine Receptors.Frontiers in cell and developmental biology · 2021Review
- Interleukin-6 Trans-signaling: A Pathway With Therapeutic Potential for Diabetic Retinopathy.Frontiers in physiology · 2021Article
- The Salmonella Secreted Effector SarA/SteE Mimics Cytokine Receptor Signaling to Activate STAT3.Cell host & microbe · 2020Article
- Review
- Activated gp130 signaling selectively targets B cell differentiation to induce mature lymphoma and plasmacytoma.JCI insight · 2019Article
- Repurposing the selective estrogen receptor modulatorEMBO molecular medicine · 2019Article
- Synthetic cytokine receptors transmit biological signals using artificial ligands.Nature communications · 2018Article
- Drug-induced modulation of gp130 signalling prevents articular cartilage degeneration and promotes repair.Annals of the rheumatic diseases · 2018Article
- Synthetic Deletion of the Interleukin 23 Receptor (IL-23R) Stalk Region Led to Autonomous IL-23R Homodimerization and Activation.Molecular and cellular biology · 2017Article
- Constitutive gp130 activation rapidly accelerates the transformation of human hepatocytes via an impaired oxidative stress response.Oncotarget · 2016Article
- The Role of Embryonic Stem Cell-expressed RAS (ERAS) in the Maintenance of Quiescent Hepatic Stellate Cells.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mode of activation of glycoprotein 130 kDa (gp130) and the transmission of the activation status through the plasma membrane are incompletely understood. In particular, the molecular function of the three juxtamembrane fibronectin III-like domains of gp130 in signal transmission remains unclear. To ask whether forced dimerization of gp130 is sufficient for receptor activation, we replaced the entire extracellular portion of gp130 with the c-jun leucine zipper region in the chimeric receptor protein L-gp130. On expression in cells, L-gp130 stimulates ligand-independent signal transducer and activator of transcription (STAT) 3 and extracellular signal-regulated kinase 1/2 phosphorylation. gp130 activation could be abrogated by the addition of a competing peptide comprising the leucine zipper region of c-fos. When stably expressed in the interleukin-3-dependent Ba/F3 murine pre-B-cells, these cells showed constitutive STAT3 activation and cytokine-independent growth over several months. Because gp130 stimulation completely suppressed differentiation of murine embryonic stem cells in vitro, we also stably expressed L-gp130 in these cells, which completely blocked their differentiation in the absence of cytokine stimulation and was consistent with high constitutive expression levels of the stem cell factor OCT-4. Thus, L-gp130 can be used in vitro and in vivo to mimic constitutive and ligand-independent activation of gp130 and STAT3, the latter of which is frequently observed in neoplastic diseases.
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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.