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Cellular assays for high-throughput screening for modulators of Trk receptor tyrosine kinases.


ABSTRACT: Trk receptor tyrosine kinases are required for signal transduction initiated by neurotrophins leading to cell proliferation, differentiation, survival and death. Alterations in Trk kinase activity have been linked to various diseases. To address the need for cell-based assays for screening and studying the selectivity of Trk kinase modulators, we developed high-throughput cell-based assays for Trk receptor kinases using nuclear factor of activated T-cells (NFAT) beta-lactamase reporter lines stably expressing full length human Trk kinases. These assays were functionally validated with cognate neurotrophin(s), inhibitors and TRK RNAi oligos and demonstrated for their utility in identifying potent and selective modulators of Trk receptor kinases.

SUBMITTER: Wang J 

PROVIDER: S-EPMC2774616 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature

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Cellular assays for high-throughput screening for modulators of Trk receptor tyrosine kinases.

Wang Jun J   Hancock Michael K MK   Dudek Jeanne M JM   Bi Kun K  

Current chemical genomics 20080225


Trk receptor tyrosine kinases are required for signal transduction initiated by neurotrophins leading to cell proliferation, differentiation, survival and death. Alterations in Trk kinase activity have been linked to various diseases. To address the need for cell-based assays for screening and studying the selectivity of Trk kinase modulators, we developed high-throughput cell-based assays for Trk receptor kinases using nuclear factor of activated T-cells (NFAT) beta-lactamase reporter lines sta  ...[more]

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