Early BDNF, NT-3, and NT-4 signaling events.
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.
Mesh Terms:
3T3 Cells, Adaptor Proteins, Signal Transducing, Animals, Brain-Derived Neurotrophic Factor, Calcium-Calmodulin-Dependent Protein Kinases, Dose-Response Relationship, Drug, Gene Expression, Humans, Isoenzymes, Membrane Proteins, Mice, Mitogen-Activated Protein Kinase 3, Mitogen-Activated Protein Kinases, Nerve Growth Factors, Neuroprotective Agents, Neurotrophin 3, Phosphatidylinositol 3-Kinases, Phospholipase C gamma, Phosphoproteins, Phosphorylation, Receptor Protein-Tyrosine Kinases, Receptor, Ciliary Neurotrophic Factor, Receptor, trkC, Receptors, Nerve Growth Factor, Signal Transduction, Transfection, Type C Phospholipases, Tyrosine, src Homology Domains
3T3 Cells, Adaptor Proteins, Signal Transducing, Animals, Brain-Derived Neurotrophic Factor, Calcium-Calmodulin-Dependent Protein Kinases, Dose-Response Relationship, Drug, Gene Expression, Humans, Isoenzymes, Membrane Proteins, Mice, Mitogen-Activated Protein Kinase 3, Mitogen-Activated Protein Kinases, Nerve Growth Factors, Neuroprotective Agents, Neurotrophin 3, Phosphatidylinositol 3-Kinases, Phospholipase C gamma, Phosphoproteins, Phosphorylation, Receptor Protein-Tyrosine Kinases, Receptor, Ciliary Neurotrophic Factor, Receptor, trkC, Receptors, Nerve Growth Factor, Signal Transduction, Transfection, Type C Phospholipases, Tyrosine, src Homology Domains
Exp Neurol
Date: Sep. 01, 1999
PubMed ID: 10486198
View in: Pubmed Google Scholar
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