Early BDNF, NT-3, and NT-4 signaling events

Exp Neurol. 1999 Sep;159(1):297-308. doi: 10.1006/exnr.1999.7148.


Much more is known about nerve growth factor (NGF) signaling than that initiated by brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), or NT-4. We sought to study early BDNF, NT-3, and NT-4 signaling events. Using TrkB-expressing cells, we found that BDNF and NT-4 individually induced tyrosine phosphorylation of TrkB in a dose-dependent fashion. At maximally effective concentrations, BDNF or NT-4 induced robust TrkB tyrosine phosphorylation at 5 min; this progressively declined at 15, 30, and 60 min. Using immunoprecipitation, PI3-kinase and tyrosine phosphorylated PLC-gamma1 and SHC were shown to be associated with tyrosine phosphorylated TrkB in response to both BDNF and NT-4. BDNF and NT-4 induced similar intensities of phosphorylation of TrkB and signaling intermediates at equivalent doses. NT-3 treatment of TrkC-expressing cells induced very similar patterns for induction of TrkC tyrosine phosphorylation and recruitment of signaling intermediates. BDNF, NT-3, and NT-4 caused rapid tyrosine phosphorylation of ERK and SNT. These data suggest that the earliest signaling events for BDNF, NT-3, and NT-4 are very similar to those for NGF.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells / chemistry
  • 3T3 Cells / physiology
  • Adaptor Proteins, Signal Transducing
  • Animals
  • Brain-Derived Neurotrophic Factor / pharmacology
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Dose-Response Relationship, Drug
  • Gene Expression / physiology
  • Humans
  • Isoenzymes / metabolism
  • Membrane Proteins / metabolism
  • Mice
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases*
  • Nerve Growth Factors / pharmacology*
  • Neuroprotective Agents / pharmacology
  • Neurotrophin 3
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phospholipase C gamma
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor, Ciliary Neurotrophic Factor
  • Receptor, trkC
  • Receptors, Nerve Growth Factor / metabolism
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology*
  • Transfection
  • Type C Phospholipases / metabolism
  • Tyrosine / metabolism
  • src Homology Domains / physiology


  • Adaptor Proteins, Signal Transducing
  • Brain-Derived Neurotrophic Factor
  • FRS2 protein, human
  • Isoenzymes
  • Membrane Proteins
  • Nerve Growth Factors
  • Neuroprotective Agents
  • Neurotrophin 3
  • Phosphoproteins
  • Receptor, Ciliary Neurotrophic Factor
  • Receptors, Nerve Growth Factor
  • Tyrosine
  • Phosphatidylinositol 3-Kinases
  • Receptor Protein-Tyrosine Kinases
  • Receptor, trkC
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • Type C Phospholipases
  • Phospholipase C gamma
  • neurotrophin 4