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Association of Transcription Factor APRF and Protein Kinase Jak1 with the Interleukin-6 Signal Transducer gp130
Abstract
Interleukin-6 (IL-6), leukemia inhibitory factor, oncostatin M, interleukin-11, and ciliary neurotrophic factor bind to receptor complexes that share the signal transducer gp130. Upon binding, the ligands rapidly activate DNA binding of acute-phase response factor (APRF), a protein antigenically related to the p91 subunit of the interferon-stimulated gene factor-3α (ISGF-3α). These cytokines caused tyrosine phosphorylation of APRF and ISGF-3α p91. Protein kinases of the Jak family were also rapidly tyrosine phosphorylated, and both APRF and Jak1 associated with gp130. These data indicate that Jak family protein kinases may participate in IL-6 signaling and that APRF may be activated in a complex with gp130.
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From The Comparative Roles of Suppressor of Cytokine Signaling-1 and -3 in the Inhibition and Desensitization of Cytokine Signaling (2006) · cites this paper as [6]
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Self-citationDominant-negative mutations in human IL6ST underlie hyper-IgE syndrome
Béziat, V., Tavernier, S. J., Chen, Y., Ma, C. S., Materna, M., Laurence, A. D. J., Staal, J., Aschenbrenner, D., Roels, L., Worley, L., et al. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20191804 · Cited by 133
“The proximal cytoplasmic region of GP130 contains two boxes that constitutively bind JAKs (Lütticken et al., 1994).”
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Mutational analysis of acute-phase response factor/Stat3 activation and dimerization
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Self-citationMajor Role of the IL17/23 Axis in Psoriasis Supports the Development of New Targeted Therapies
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“A similar phosphorylation-induced change in electrophoretic mobility was reported for the native gp130, which showed an increase in the apparent molecular mass from ; 155 to ;170 kDa (30).”
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“These kinases, either alone or in conjunction with each other, appear to be responsible for effects mediated by several cytokines and neurokines (2, 12, 17, 22, 30, 31, 35).”
BackgroundEstrogen augments glucose transporter and IGF1 expression in primate cerebral cortex
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Differentiation-regulated serine phosphorylation of STAT1 promotes GAF activation in macrophages
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“Regulated Ser phosphorylation has recently been suggested to affect the dimer formation or transactivation potential of STAT3, a family memberresponsivetosignalingbythegp130cytokinereceptor subunit (19, 20 , 40).”
BackgroundSelf-citationA Stat3-interacting protein (StIP1) regulates cytokine signal transduction
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Self-citationCiliary neurotrophic factor: A review
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c-Src and IL-6 inhibit osteoblast differentiation and integrate IGFBP5 signalling
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“The major step in IL-6-type cytokine signalling is the rapid activation of the Janus family tyrosine kinases (JAK proteins) by binding to the signal transducing proteins gp130, LIF receptor and OSM recepto”
BackgroundTumor Microenvironment Promotes Cancer Progression, Metastasis, and Therapeutic Resistance
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In Vivo and In Vitro Activities of the gp130-Stimulating Designer Cytokine Hyper-IL-6
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“A very early event is tyrosine phosphorylation of the 92kDa STAT3 protein by JAK1 or JAK2 kinase (7, 8).”
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“It has been reported that among the seven members of the Stat family, Stat3 is the major mediator of gp130 signals (Raz et al., 1994; Lütticken et al., 1994).”
BackgroundTargeting STAT3 Signaling Pathway in Colorectal Cancer
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“Members of the Jak family of kinases can mediate the phosphorylation of Stat proteins on a single tyrosine leading to Stat translocation and DNA binding [22–28].”
Background
Metadata
- Authors
- Lütticken, C., Wegenka, U. M., Yuan, J., Buschmann, J., Schindler, C., Ziemiecki, A., Harpur, A. G., Wilks, A. F., Yasukawa, K., Taga, T., Kishimoto, T., Barbieri, G., Pellegrini, S., Sendtner, M., Heinrich, P. C., & Horn, F.
- Affiliations
- RWTH Aachen University (DE)
- ORCID
- Venue
- Science
- Published
- 1994-01-07
- Volume
- 263
- Issue
- 5143
- Pages
- 89-92
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1999028040
- Cited by
- 814
- References
- 0
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 11 · 2023: 5 · 2022: 7 · 2021: 13 · 2020: 10 · 2019: 14 · 2018: 14 · 2017: 17 · 2016: 17 · 2015: 23 · 2014: 15 · 2013: 15 · 2012: 20
- FWCI
- 38.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- RWTH Publications (RWTH Aachen) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- JAK1, gp130, IL-6 signaling, cytokine-receptor complex, tyrosine phosphorylation, transcription factor activation, leukemia inhibitory factor, oncostatin M, interleukin-11, ciliary neurotrophic factor, signal transduction
- MeSH terms
- Base Sequence, DNA-Binding Proteins, Humans, Interferon-gamma, Membrane Glycoproteins, Molecular Sequence Data, Phosphorylation, Protein-Tyrosine Kinases, Transcription Factors, Tumor Cells, Cultured, Tyrosine, Signal Transduction, Trans-Activators, Antigens, CD, Interleukin-6, Cytokines, STAT1 Transcription Factor, STAT3 Transcription Factor, Cytokine Receptor gp130, Interferon-Stimulated Gene Factor 3, Interferon-Stimulated Gene Factor 3, gamma Subunit, Janus Kinase 1
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