The low affinity NGF receptor, p75, can collaborate with each of the Trks to potentiate functional responses to the neurotrophins

Neuron. 1994 Jul;13(1):187-201. doi: 10.1016/0896-6273(94)90469-3.

Abstract

NGF and the other neurotrophins all bind to the low affinity NGF receptor (LNGFR). Although early studies suggested that the LNGFR was absolutely required for the formation of a functional neurotrophin receptor, current evidence indicates that the Trk family of receptor tyrosine kinases, in the absence of the LNGFR, can directly bind to and mediate responses to the neurotrophins. Here we describe a functional approach, in fibroblasts, designed to assay for the ability of the LNGFR to potentiate Trk-mediated responses to the neurotrophins. We report that although collaboration between the LNGFR and the Trks could be detected in this system, a truncated form of the LNGFR displayed a much more dramatic ability to interact functionally with each of the Trks, potentiating masked autocrine loops as well as responses to limiting amounts of exogenously provided neurotrophins.

MeSH terms

  • 3T3 Cells
  • Animals
  • Base Sequence
  • Brain-Derived Neurotrophic Factor
  • Gene Expression
  • Humans
  • Mice
  • Molecular Sequence Data
  • Mutagenesis
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / metabolism
  • Nerve Growth Factors / pharmacology*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / pharmacology
  • Neurotrophin 3
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Receptors, Nerve Growth Factor / chemistry
  • Receptors, Nerve Growth Factor / genetics
  • Receptors, Nerve Growth Factor / physiology*
  • Structure-Activity Relationship
  • Transfection

Substances

  • Brain-Derived Neurotrophic Factor
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Neurotrophin 3
  • Receptors, Nerve Growth Factor
  • Receptor Protein-Tyrosine Kinases