کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8419782 | 1545752 | 2010 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A receptor-independent, cell-based JAK activation assay for screening for JAK3-specific inhibitors
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کلمات کلیدی
GM-CSFTELJAK3 inhibitorMitogen-activated protein kinase/extracellular signal-regulated kinase kinaseJanus kinase - کیناز جانوس STAT - آمارinterleukin - اینترلوکینCommon γ chain - زنجیره γ معمولیgranulocyte macrophage colony-stimulating factor - ماکروفاژ گرانولوسیت عامل کلونی تحریک کنندهSignal transducer and activator of transcription - مبدل سیگنال و فعال کننده رونویسیMEK - مجاهدین خلقJAK - چگونه
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیوتکنولوژی یا زیستفناوری
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چکیده انگلیسی
New immunosuppressive compounds with less systemic toxicity that could replace calcineurin inhibitors are urgently needed. For identification of specific inhibitors of JAK3, a potential new drug target, from large chemical libraries we developed a cell-based screening system. TEL-JAK fusion proteins composed of an oligomerization domain of TEL and kinase and/or pseudokinase domains of JAKs provided constitutive activation of JAKs without receiving a signal from the cytokine receptors. These fusion proteins also induced STAT5b phosphorylation in the absence of cytokine receptors. Both the kinase and pseudokinase domains of JAKs were required for full activation of the JAKs, and four copies of STAT5 response elements provided the greatest luciferase activity. The sensitivity and specificity of the system was evaluated using specific JAK3, JAK2, or MEK inhibitors. Thus, we generated a receptor-independent, cell-based selective screening system for specific JAK3 inhibitors, which is easily convertible to a high-throughput screening platform.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Immunological Methods - Volume 354, Issues 1â2, 31 March 2010, Pages 45-52
Journal: Journal of Immunological Methods - Volume 354, Issues 1â2, 31 March 2010, Pages 45-52
نویسندگان
Keunhee Oh, Kyeung Min Joo, Yong Sik Jung, Jaehwan Lee, Heonjoong Kang, Hee-Yoon Lee, Dong-Sup Lee,