ArticleThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology2009
Janus Kinase 2 Inhibitor AG490 Inhibits the STAT3 Signaling Pathway by Suppressing Protein Translation of gp130.
Article in The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 26 citations in OpenAlex.
- Leptin Promotes Vasculogenic Mimicry in Breast Cancer Cells by Regulating Aquaporin-1.International journal of molecular sciences · 2024Article
- Natural STAT3 Inhibitors for Cancer Treatment: A Comprehensive Literature Review.Recent patents on anti-cancer drug discovery · 2024Review
- Nicotine Activating αMolecular neurobiology · 2022Article
- Granulocyte colony-stimulating factor attenuates myocardial remodeling and ventricular arrhythmia susceptibility via the JAK2-STAT3 pathway in a rabbit model of coronary microembolization.BMC cardiovascular disorders · 2020Article
- Neuroprotective Effects of AG490 in Neonatal Hypoxic-Ischemic Brain Injury.Molecular neurobiology · 2019Article
- The influence of central interleukin-6 on behavioral changes associated with acute alcohol intoxication in adult male rats.Alcohol (Fayetteville, N.Y.) · 2019Article
- Inhibition of the Interleukin-11-STAT3 Axis Attenuates Hypoxia-Induced Migration and Invasion in MDA-MB-231 Breast Cancer Cells.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2014Article
- Effects of AG490 and S3I-201 on regulation of the JAK/STAT3 signaling pathway in relation to angiogenesis in TRAIL-resistant prostate cancer cellsOncology letters · 2014Article
- Electroacupuncture effects on cortical neurons, as well as Janus kinase 2-signal transducer and activator of transcription 3 signal transduction pathway, in a rat model of cerebral ischemia.Neural regeneration research · 2012Article
- Free fatty acid palmitate impairs the vitality and function of cultured human bladder smooth muscle cells.PloS one · 2012Article
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Authors and funding
7 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
The binding of interleukin-6 (IL-6) cytokine family ligands to the gp130 receptor complex activates the Janus kinase (JAK)/ signal transducer and activator of transcription 3 (STAT3) signal transduction pathway, where STAT3 plays an important role in cell survival and tumorigenesis. Constitutive activation of STAT3 has been frequently observed in many cancer tissues, and thus, blocking of the gp130 signaling pathway, at the JAK level, might be a useful therapeutic approach for the suppression of STAT3 activity, as anticancer therapy. AG490 is a tyrphostin tyrosine kinase inhibitor that has been extensively used for inhibiting JAK2 in vitro and in vivo. In this study, we demonstrate a novel mechanism associated with AG490 that inhibits the JAK/STAT3 pathway. AG490 induced downregulation of gp130, a common receptor for the IL-6 cytokine family compounds, but not JAK2 or STAT3, within three hours of exposure. The downregulation of gp130 was not caused by enhanced degradation of gp130 or by inhibition of mRNA transcription. It most likely occurred by translation inhibition of gp130 in association with phosphorylation of the eukaryotic initiation factor-2alpha . The inhibition of protein synthesis of gp130 by AG490 led to immediate loss of mature gp130 in cell membranes, due to its short half-life, thereby resulting in reduction in the STAT3 response to IL-6. Taken together, these results suggest that AG490 blocks the STAT3 activation pathway via a novel pathway.
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