Abstract
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.
Copyright 1999 Academic Press.
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
Substances
-
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