A receptor-independent, cell-based JAK activation assay for screening for JAK3-specific inhibitors

Cited 2 time in webofscience Cited 0 time in scopus
  • Hit : 285
  • Download : 0
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. (C) 2010 Elsevier B.V. All rights reserved.
Publisher
ELSEVIER SCIENCE BV
Issue Date
2010-03
Language
English
Article Type
Article
Keywords

COMMON GAMMA-CHAIN; T-CELLS; ALLOGRAFT SURVIVAL; BINDING-SITE; IMMUNOSUPPRESSION; KINASE; PROTEINS; UNRESPONSIVENESS; CP-690,550; REJECTION

Citation

JOURNAL OF IMMUNOLOGICAL METHODS, v.354, no.1-2, pp.45 - 52

ISSN
0022-1759
DOI
10.1016/j.jim.2010.01.010
URI
http://hdl.handle.net/10203/98490
Appears in Collection
CH-Journal Papers(저널논문)
Files in This Item
There are no files associated with this item.
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 2 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0