Cited by 122Cytokine Signaling Pathways and InteractionsReceptor Mechanisms and SignalingNF-κB Signaling Pathways

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Molecular basis of the cell specificity of cytokine action

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Ishihara, Katsuhiko, Hirano, Toshio·2002·Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Abstract

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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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)
DOI: 10.1016/s0167-4889(02)00321-x
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 3912 d)
Locations: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research (publishedVersion)
PubMed (publishedVersion)
Funders: Ministry of Education, Culture, Sports, Science and Technology
Topics: Life Sciences › Immunology and Microbiology › Immunology › 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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Molecular basis of the cell specificity of cytokine action

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