Molecular basis of the cell specificity of cytokine action
Open accessAbstract
The molecular cloning and biological analyses of cytokines have led us to a general understanding of their pleiotropism and redundancy. These features have been ascribed to the composition of cytokine receptor complexes, which include a signal-transducing receptor subunit that is used by all members of a cytokine family and a binding subunit that is specific for each cytokine. Even though a given cytokine uses the same receptor complex when binding to various cell types, the cytokine elicits quite specific and distinct biological responses in different types of cells. Even in the same type of cell, the responses to a given cytokine could vary depending on the location of the cell and the condition of its microenvironment. Important mediators for the main cytokine signal-transduction pathway are the Janus kinases (Jaks) and signal transducer and activator of transcription (STATs). Selective usage of members of the Jak and STAT families by a given cytokine receptor is partly responsible for the specificity of cytokine action. In addition to the Jak-STAT pathway, a cytokine receptor complex can simultaneously operate multiple signal-transduction pathways, which usually express contradictory properties. These contradictory signals from a single cytokine are orchestrated to evoke a unified biological response in the cell. Here we discuss the molecular mechanisms that regulate how the cell specificity of cytokine signals is regulated, especially focusing on the IL-6/gp130 system.
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IL-6 binds membrane-bound IL-6 receptor α (gp80), and the IL-6-gp80 dimer interacts with gp130, the signal transducing unit.
“For signal transduction, IL-6 binds the membrane-bound IL-6 receptor α (gp80). The IL-6-gp80 dimer interacts with gp130, the signal transducing unit in this complex.”
From The IL-6–gp130–STAT3 pathway in hepatocytes triggers liver protection in T cell–mediated liver injury (2005) · cites this paper as [19]
Section 2 (page unavailable) says IL-6 binds IL-6Rα, triggering its association with gp130, which the paper identifies as the signal-transducing subunit. The paper distinguishes cell-expressed IL-6Rα from its soluble form, but the available passages do not identify IL-6Rα as “gp80”; that specific label is unsupported by our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measuredIL-6 activates intracellular pathways via the gp130 receptor.
“IL-6 activates intracellular pathways via the gp130 receptor.”
From The IL-6–gp130–STAT3 pathway in hepatocytes triggers liver protection in T cell–mediated liver injury (2005) · cites this paper as [19]
gp130 is the common signal transducer used by the IL-6 family of cytokines.
“Gp130 is the common signal transducer used by the IL-6 family of cytokines, which includes IL-6, leukemia inhibitory factor (LIF), IL-11, cardiotrophin-1 (CT-1), oncostatin-M (OSM), and the ciliary neurotrophic factor (19).”
From The IL-6–gp130–STAT3 pathway in hepatocytes triggers liver protection in T cell–mediated liver injury (2005) · cites this paper as [19]
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- Authors
- Ishihara, K., & Hirano, T.
- Affiliations
- The University of Osaka (JP)
- RIKEN (JP)
- Corresponding author
- Hirano, Toshio
- ORCID
- Ishihara, Katsuhiko
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
- Publisher
- Elsevier BV
- Published
- 2002-11
- Volume
- 1592
- Issue
- 3
- Pages
- 281-296
- ISSN
- 0167-4889 (ISSN-L)
- OpenAlex
- W2143163223
- Cited by
- 122
- References
- 101
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 8 · 2019: 7 · 2018: 8 · 2017: 2 · 2016: 2 · 2015: 3 · 2014: 4 · 2013: 7 · 2012: 7
- FWCI
- 0.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- cytokine-receptor complex, Janus kinase, STAT proteins, JAK/STAT signaling, cytokine redundancy, signal transduction
- MeSH terms
- Animals, B-Lymphocytes, Binding Sites, Cell Communication, Cell Line, Cell Nucleus, Cytosol, Enzyme Activation, Humans, Membrane Glycoproteins, Phosphoproteins, Thymus Gland, Signal Transduction, Antigens, CD, Cytokines, Receptors, Cytokine, Receptors, Interleukin-6, Receptor Cross-Talk, Mitogen-Activated Protein Kinases, Adaptor Proteins, Signal Transducing, Cytokine Receptor gp130
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