ArticleThe Journal of biological chemistry
Interleukin-6 controls recycling and degradation, but not internalization of its receptors.
Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Article
- The PVAT-MAMs Axis in Atherosclerosis: A Hypothesis-Driven Cross-Scale Conceptual Framework.International journal of molecular sciences · 2026Review
- Cold, Hot, and Lethal-The Tumour Microenvironment and the Immunology of Head and Neck Squamous Cell Carcinoma.International journal of molecular sciences · 2025Review
- No evidence for paradoxical effects of tocilizumab in rodents.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- SNX17 mediates STAT3 activation to promote hepatocellular carcinoma progression via a retromer dependent mechanism.International journal of biological sciences · 2025Article
- Small protein blockers of human IL-6 receptor alpha inhibit proliferation and migration of cancer cells.Cell communication and signaling : CCS · 2024Article
- Targeting IL-6 trans-signalling: past, present and future prospects.Nature reviews. Immunology · 2023Review
- Article
- Molecular and cellular factors determining the functional pleiotropy of cytokines.The FEBS journal · 2023Review
- Article
- Interleukin-6 transiently promotes proliferation of osteoclast precursors and stimulates the production of inflammatory mediators.Molecular biology reports · 2022Article
- β-Klotho promotes glycolysis and glucose-stimulated insulin secretion via GP130.Nature metabolism · 2022Article
- Interleukin-6 receptor alpha and CD27 discriminate intratumoral T helper 17 subpopulations with distinct functional properties in a mouse lung cancer model.Immunity, inflammation and disease · 2021Article
- Role of IL-6 in the commitment of T cell subsets.Cytokine · 2021Review
- Endosomes as Signaling Platforms for IL-6 Family Cytokine Receptors.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interleukin-6 (IL-6) is a cytokine implicated in proinflammatory as well as regenerative processes and acts via receptor complexes consisting of the ubiquitously expressed, signal-transducing receptor gp130 and the IL-6 receptor (IL-6R). The IL-6R is expressed only on hepatocytes and subsets of leukocytes, where it mediates specificity of the receptor complex to IL-6 as the subunit gp130 is shared with all other members of the IL-6 cytokine family such as IL-11 or IL-27. The amount of IL-6R at the cell surface thus determines the responsiveness of the cell to the cytokine and might therefore be decisive in the development of inflammatory disorders. However, how the expression levels of IL-6R and gp130 at the cell surface are controlled is largely unknown. Here, we show that IL-6R and gp130 are constitutively internalized independent of IL-6. This process depends on dynamin and clathrin and is temporally controlled by motifs within the intracellular region of gp130 and IL-6R. IL-6 binding and internalization of the receptors is a prerequisite for activation of the Jak/STAT signaling cascade. Targeting of gp130, but not of the IL-6R, to the lysosome for degradation depends on stimulation with IL-6. Furthermore, we show that after internalization and activation of signaling, both the IL-6R and gp130 are recycled back to the cell surface, a process that is enhanced by IL-6. These data reveal an important function of IL-6 beyond the pure activation of signaling.
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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.