The rat trkC locus encodes multiple neurogenic receptors that exhibit differential response to neurotrophin-3 in PC12 cells

Pantelis Tsoulfas, Dan Soppet, Enrique Escandon, Lino Tessarollo, José Luis Mendoza-Ramirez, Arnon Rosenthal, Karoly Nikolics, Luis F. Parada

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Abstract

Members of the Trk tyrosine kinase family have recently been identified asfunctional receptors of the NGF family of neurotrophins. Here we show the rat trkC locus to be complex, encoding at least four distinct polypeptides. Three of the encoded polypeptides are full-length receptor tyrosine kinases that differ by novel amino acid insertions in the kinase domain. A fourth protein is a truncated receptor that lacks the catalytic domain. Tyrosine phosphorylation, cross-linking, and ligand binding assays indicate that TrkC receptors interact with NT-3 and not with the related neurotrophins NGF, BDNF, xNT-4, or hNT-5. Furthermore, high and low affinity NT-3-binding sites are associated with the TrkC receptors. Stable and transient expression of TrkC receptors in PC 12 cells indicates that the neurite outgrowth response elicited by NT-3 is dramatic in receptors lacking the novel kinase insert (gpl50trkC but absent in receptors containing the 14 amino acid insert in the kinase domain (gp150trkC14). These data suggest that the trkC locus encodes receptors that may be capable of mediating different biological responses within the cell. This could have important implications in understanding the role of neurotrophins in the development of the vertebrate nervous system.

Original languageEnglish (US)
Pages (from-to)975-990
Number of pages16
JournalNeuron
Volume10
Issue number5
DOIs
StatePublished - May 1993

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ASJC Scopus subject areas

  • Neuroscience(all)

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Tsoulfas, P., Soppet, D., Escandon, E., Tessarollo, L., Mendoza-Ramirez, J. L., Rosenthal, A., Nikolics, K., & Parada, L. F. (1993). The rat trkC locus encodes multiple neurogenic receptors that exhibit differential response to neurotrophin-3 in PC12 cells. Neuron, 10(5), 975-990. https://doi.org/10.1016/0896-6273(93)90212-A