Human trks: molecular cloning, tissue distribution, and expression of extracellular domain immunoadhesins

Abstract

Using molecular cloning techniques, human homologs of the known members of the trk family of neurotrophin receptors have been cloned and sequenced. Overall, there is a high degree of similarity between the human sequences and those from other mammals; however, there are differences in splicing patterns. There are two spliced forms of the extracellular domain of trkC in the human, a finding that has not been described in other species. In contrast, fewer spliced forms were detected of the intracellular domains of human trkB and trkC than has been described in other mammals. Northern analysis and in situ hybridization experiments indicate that the human trks are expressed in a similar pattern to that described in other mammals. Expression of the trk extracellular domains as fusion proteins with IgG heavy chain yields soluble molecules that mimic intact trks in their binding specificity and affinity. These soluble chimeras block the biological activity of their cognate neurotrophin(s) in vitro.

Expression of mRNA for the neurotrophin receptor trkC in neuroblastomas with favourable tumour stage and good prognosis

“…Brain-derived neurotrophic factor (BDNF) (Barde et al, 1982;Leibrock et al, 1989) (Nakagawara et al, 1994). In this study we have investigated the mRNA expression profile of the third member of the neurotrophin receptor tyrosine kinase family, trkC, a receptor for neurotrophin-3 (NT-3) (Lamballe et al, 1991) which is involved in the survival of subpopulations of neural crest and placodederived sensory neurons (Ernfors et al, 1994 (Shelton et al, 1995) which was identical to that of our clone in the transmembrane region. Initial Northern blot analysis showed that levels of trkC mRNA were below the detection limit in most samples.…”

“…A relapsing stage 1 tumour showed a relatively low level of trkC expression (no. 24, Figure 2 the human trkC receptor (Shelton et al, 1995 (Hoehner et al, 1995). It was found that the more differentiated tumour cells stained most intensely for trkC but there was no significant correlation with tumour stage or patient prognosis.…”

Exercise decreases myelin‐associated glycoprotein expression in the spinal cord and positively modulates neuronal growth

“…BDNF was selectively sequestered during exercise using a specific immunoadhesin chimera (TrkB-IgG, R&D System, Minneapolis, MN), which comprises the extracellular domains of human TrkB and the Fc domain of immunoglobulin G (IgG), and has been shown to specifically antagonize BDNF action (Shelton et al, 1995). Infusion of TrkB-IgGs was achieved by coupling them to microbeads (Lumaflour Corp., Naples, FL), which we have previously used as a reservoir for the successful delivery of viable inhibitors into the hippocampus (Vaynman et al, 2003).…”

Neurotrophins and B-cell malignancies

“…TrkB.T2 does not appear to have signaling ability and has not been found in humans [74]. TrkB 95 , though lacking the catalytic kinase domain, still retains some signalling ability of its own [75].…”