Cellular Assays for High-Throughput Screening for Modulators of Trk Receptor Tyrosine Kinases
Jun Wang, Michael K Hancock, Jeanne M Dudek, Kun Bi*
Identifiers and Pagination:Year: 2008
First Page: 27
Last Page: 33
Publisher Id: CCGTM-1-27
Article History:Received Date: 20/12/2007
Revision Received Date: 12/1/2008
Acceptance Date: 21/1/2008
Electronic publication date: 25/2/2008
Collection year: 2008
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.