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

Much more is known about nerve growth factor (NGF) signaling than that init iated by brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), o r NT-4. We sought to study early BDNF, NT-3, and NT-4 signaling events, Usi ng 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 phospho rylation at 5 min; this progressively declined at 15, 30, and 60 min. Using immunoprecipitation, PIS-kinase and tyrosine phosphorylated PLC-gamma 1 an d SHC were shown to be associated with tyrosine phosphorylated TrkB in resp onse to both BDNF and NT-4. BDNF and NT-4 induced similar intensities of ph osphorylation of TrkB and signaling intermediates at equivalent doses. NT-3 treatment of TrkC-expressing cells induced very similar patterns for induc tion of TrkC tyrosine phosphorylation and recruitment of signaling intermed iates. BDNF, NT-3, and NT-4 caused rapid tyrosine phosphorylation of ERK an d SNT. These data suggest that the earliest signaling events for BDNF, NT-3 , and NT-4 are very similar to those for NGF. (C) 1999 Academic Press.