ArticleThe Biochemical journal2002
Structural requirements of the interleukin-6 signal transducer gp130 for its interaction with Janus kinase 1: the receptor is crucial for kinase activation.
Article in The Biochemical journal, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 64 citations in OpenAlex.
- Recent Insights Into Targeting Interleukin-27 in Coronary Artery Disease.Journal of cardiovascular translational research · 2025Review
- What can we learn from treatments of oral lichen planus?Frontiers in cellular and infection microbiology · 2024Review
- Inhibition of GP130/STAT3 and EMT by combined bazedoxifene and paclitaxel treatment in ovarian cancer.Oncology reports · 2022Article
- The effect of a fennel seed extract on the STAT signaling and intestinal barrier function.PloS one · 2022Article
- Article
- The Janus Kinase (JAK) FERM and SH2 Domains: Bringing Specificity to JAK-Receptor Interactions.Frontiers in endocrinology · 2017Review
- A Role for Soluble IL-6 Receptor in Osteoarthritis.Journal of functional morphology and kinesiology · 2017Article
- Crystal Structure of a Complex of the Intracellular Domain of Interferon λ Receptor 1 (IFNLR1) and the FERM/SH2 Domains of Human JAK1.Journal of molecular biology · 2016Article
- The Structural Basis for Class II Cytokine Receptor Recognition by JAK1.Structure (London, England : 1993) · 2016Article
- Structural basis of recognition of interferon-α receptor by tyrosine kinase 2.Nature structural & molecular biology · 2014Article
- Identification of a novel function of the clathrin-coated structure at the plasma membrane in facilitating GM-CSF receptor-mediated activation of JAK2.Cell cycle (Georgetown, Tex.) · 2012Article
- Evolution of JAK-STAT pathway components: mechanisms and role in immune system development.PloS one · 2012Article
- Three lysine residues in the common β chain of the interleukin-5 receptor are required for Janus kinase (JAK)-dependent receptor ubiquitination, endocytosis, and signaling.The Journal of biological chemistry · 2011Article
- The use of structural biology in Janus kinase targeted drug discovery.Current drug targets · 2011Review
- Structural snapshots of full-length Jak1, a transmembrane gp130/IL-6/IL-6Rα cytokine receptor complex, and the receptor-Jak1 holocomplex.Structure (London, England : 1993) · 2011Article
- Jak/STAT pathways in cytokine signaling and myeloproliferative disorders: approaches for targeted therapies.Genes & cancer · 2010Article
- Perspectives for the use of structural information and chemical genetics to develop inhibitors of Janus kinases.Journal of cellular and molecular medicine · 2010Review
- Hematopoietic cytokine receptor signaling.Oncogene · 2007Review
- Principles of interleukin (IL)-6-type cytokine signalling and its regulation.The Biochemical journal · 2003Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We analysed the interaction of gp130, the common signal-transducing receptor chain of interleukin (IL)-6 type cytokines, with Jak1, the Janus family kinase which is crucial for signal transduction of this group of cytokines. With a truncated chimaeric IL-5Rbeta-gp130 receptor expressed in COS-7 cells, we show that the membrane-proximal 69 amino acids are sufficient to mediate Jak1 binding and activation. Deletion of box2 drastically reduced binding of endogenous, but not of overexpressed, Jak1. Several point mutations in the membrane-proximal region of gp130 (W652A, P671/P672A, F676A, Y683F, where W, A, P, F and Y are tryptophan, alanine, proline, phenylalanine and tyrosine) did not affect Jak1 association. However, stimulation of chimaeric receptors with the mutations P671/P672A and F676A in the interbox1/box2 region resulted in a reduced activation of STAT (signal transducer and activator of transcription) transcription factors. Most importantly, signalling by the receptor with the box1 mutation W652A was totally abrogated. Although this mutation did not affect Jak1 association, stimulation-dependent phosphorylation of Jak1 was prevented. The W652 mutation acts dominantly, since no signalling occured even when only a single cytoplasmic chain of a gp130 dimer contained the mutation. Our data demonstrate that the mere proximity of Jaks in an activated receptor complex is not sufficient to mediate their activation. Rather, it seems that parts of the receptor, including the box1 region, are involved in positioning Jaks correctly so that ligand-induced receptor dimerization and reorientation can lead to their mutual activation and subsequently to downstream signalling events.
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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.