HUMAN TRKS - MOLECULAR-CLONING, TISSUE DISTRIBUTION, AND EXPRESSION OF EXTRACELLULAR DOMAIN IMMUNOADHESINS

Using molecular cloning techniques, human homologs of the known member s of the trk family of neurotrophin receptors have been cloned and seq uenced. Overall, there is a high degree of similarity between the huma n sequences and those from other mammals; however, there are differenc es in splicing patterns. There are two spliced forms of the extracellu lar domain of trkC in the human, a finding that has not been described in other species. In contrast, fewer spliced forms were detected of t he intracellular domains of human trkB and trkC than has been describe d in other mammals. Northern analysis and in situ hybridization experi ments indicate that the human trks are expressed in a similar pattern to that described in other mammals. Expression of the trk extracellula r domains as fusion proteins with IgG heavy chain yields soluble molec ules that mimic intact trks in their binding specificity and affinity. These soluble chimeras block the biological activity of their cognate neurotrophin(s) in vitro.