TY - JOUR
T1 - The rat trkC locus encodes multiple neurogenic receptors that exhibit differential response to neurotrophin-3 in PC12 cells
AU - Tsoulfas, Pantelis
AU - Soppet, Dan
AU - Escandon, Enrique
AU - Tessarollo, Lino
AU - Mendoza-Ramirez, José Luis
AU - Rosenthal, Arnon
AU - Nikolics, Karoly
AU - Parada, Luis F.
N1 - Funding Information:
We thank Drs. T. Jessell, N. Nakanishi, C. Ib~Eez, H. Persson, and D. Morrison for providing reagents and D. Loeb and L. Greene for helpful suggestions. We are grateful to the members of the Mammalian Genetics Laboratory for support and encouragement and T. Copeland and P. Wesdock of the Protein Structure Working Group for generating peptides. We thank Dr. J. Pickel for critical review of the manuscript, Drs. Y. Ohshima and M. Koga (Kyushu University) for communicating their unpublished results, R. Frederickson for help in preparation of the figures, and Cindy Fitzpatrick for help in preparation of the manuscript. D. S. is supported by a postdoctoral fellowship from the Foundation for Advanced Cancer Studies, Inc. This research was sponsored in part by the National Cancer Institute, DHHS, under contract N01-C0-74101 with ABE The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC Section 1734 solely to indicate this fact.
PY - 1993/5
Y1 - 1993/5
N2 - 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.
AB - 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.
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U2 - 10.1016/0896-6273(93)90212-A
DO - 10.1016/0896-6273(93)90212-A
M3 - Article
C2 - 8494648
AN - SCOPUS:0027161499
SN - 0896-6273
VL - 10
SP - 975
EP - 990
JO - Neuron
JF - Neuron
IS - 5
ER -