Current Chemical Genomics and Translational Medicine

2008, 1 : 27-33
Published online 2008 February 25. DOI: 10.2174/1875397300801010027
Publisher ID: CCGTM-1-27

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

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

* 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.