RESEARCH ARTICLE


Cellular Assays for High-Throughput Screening for Modulators of Trk Receptor Tyrosine Kinases



Jun Wang, Michael K Hancock, Jeanne M Dudek, Kun Bi*
Invitrogen Corporation, Discovery Sciences, 501 Charmany Drive, Madison, WI 53719, USA


Article Metrics

CrossRef Citations:
0
Total Statistics:

Full-Text HTML Views: 719
Abstract HTML Views: 445
PDF Downloads: 197
Total Views/Downloads: 1361
Unique Statistics:

Full-Text HTML Views: 277
Abstract HTML Views: 247
PDF Downloads: 129
Total Views/Downloads: 653



2008 Bentham Science Publishers Ltd.

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.

* Address correspondence to this author at the Invitrogen Corporation, Discovery Sciences, 501 Charmany Drive, Madison, WI 53719, USA; E-mail: Kun.Bi@invitrogen.com


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.