CDB15:0001159 NTF3 — NTRK3
Experimentally validated in Human; Orthology-inferred in Mouse, Rat, Frog, Zebrafish, Chicken, Macaque, Pig, Dog, Cow, Chimp, Horse, Marmoset, Sheep
Title
Journal:; Year Published:
Abstract
Similarities and differences in the way neurotrophins interact with the Trk receptors in neuronal and nonneuronal cells.
Neuron, 1993; PubMed, Homo sapiens NTF3 — Homo sapiens NTRK3
ABSTRACT: We have exploited a battery of approaches to address several controversies that have accompanied the expansion of the nerve growth factor (NGF) family of neurotrophic factors and the identification of the Trk tyrosine kinases as receptors for these factors. For example, we find that a recently cloned mammalian neurotrophin, known as either neurotrophin-4 or neurotrophin-5 and assigned widely differing receptor specificities, represents the functional counterpart of Xenopus neurotrophin-4 and is a "preferred" ligand for TrkB. However, its interactions with TrkB can be distinguished from those of brain-derived neurotrophic factor (BDNF) with TrkB. We also find that all of the Trks display similar dose responses to their "preferred" ligands in neuronal as compared with nonneuronal cells (i.e., NGF for TrkA, BDNF and NT-4/5 for TrkB, and NT-3 for TrkC), providing evidence against a role for accessory molecules expressed in neurons in generating receptors that would allow for responses to lower concentrations of the neurotrophins. However, we find that a neuronal environment does restrict the Trks in their ability to respond to their "nonpreferred" neurotrophin ligands.
High resolution mapping of the binding site of TrkA for nerve growth factor and TrkC for neurotrophin-3 on the second immunoglobulin-like domain of the Trk receptors.
The Journal of biological chemistry, 1998; PubMed, Homo sapiens NTF3 — Homo sapiens NTRK3
ABSTRACT: Neurotrophic factors are important for survival and maintenance of neurons during developmental and adult stages of the vertebrate nervous system. The neurotrophins mediate their signal into the cell by specific interaction with tyrosine kinase receptors of the Trk family. The extracellular immunoglobulin-like domain of the Trk receptors adjacent to the membrane has previously been shown to be the dominant element for specific neurotrophin binding. Using computer graphics models of the human TrkA and TrkC immunoglobulin-like domains as a guide, the residues involved in binding to their respective neurotrophins were mapped by mutational analysis. TrkC primarily utilizes loop EF, between beta-strands E and F, for binding. In contrast, TrkA utilizes the EF loop as well as additional residues, the latter being prime candidates for determining the specificity of TrkA versus TrkC. When selected TrkC and TrkA mutants with reduced binding were expressed on NIH3T3 cells, neurotrophin-induced autophosphorylation was strongly reduced or absent.