PMID- 10486198 OWN - NLM STAT- MEDLINE DCOM- 19991007 LR - 20161124 IS - 0014-4886 (Print) IS - 0014-4886 (Linking) VI - 159 IP - 1 DP - 1999 Sep TI - Early BDNF, NT-3, and NT-4 signaling events. PG - 297-308 AB - 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. CI - Copyright 1999 Academic Press. FAU - Yuen, E C AU - Yuen EC AD - Department of Neurology, University of Washington, Seattle, Washington, 98195, USA. FAU - Mobley, W C AU - Mobley WC LA - eng GR - AG00649/AG/NIA NIH HHS/United States GR - NS24054/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Exp Neurol JT - Experimental neurology JID - 0370712 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (FRS2 protein, human) RN - 0 (Isoenzymes) RN - 0 (Membrane Proteins) RN - 0 (Nerve Growth Factors) RN - 0 (Neuroprotective Agents) RN - 0 (Neurotrophin 3) RN - 0 (Phosphoproteins) RN - 0 (Receptor, Ciliary Neurotrophic Factor) RN - 0 (Receptors, Nerve Growth Factor) RN - 42HK56048U (Tyrosine) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (Receptor, trkC) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 3.1.4.- (Type C Phospholipases) RN - EC 3.1.4.3 (Phospholipase C gamma) RN - P658DCA9XD (neurotrophin 4) SB - IM MH - 3T3 Cells/chemistry/physiology MH - Adaptor Proteins, Signal Transducing MH - Animals MH - Brain-Derived Neurotrophic Factor/pharmacology MH - Calcium-Calmodulin-Dependent Protein Kinases/metabolism MH - Dose-Response Relationship, Drug MH - Gene Expression/physiology MH - Humans MH - Isoenzymes/metabolism MH - Membrane Proteins/metabolism MH - Mice MH - Mitogen-Activated Protein Kinase 3 MH - *Mitogen-Activated Protein Kinases MH - Nerve Growth Factors/*pharmacology MH - Neuroprotective Agents/pharmacology MH - Neurotrophin 3 MH - Phosphatidylinositol 3-Kinases/metabolism MH - Phospholipase C gamma MH - Phosphoproteins/metabolism MH - Phosphorylation MH - Receptor Protein-Tyrosine Kinases/metabolism MH - Receptor, Ciliary Neurotrophic Factor MH - Receptor, trkC MH - Receptors, Nerve Growth Factor/metabolism MH - Signal Transduction/*drug effects/*physiology MH - Transfection MH - Type C Phospholipases/metabolism MH - Tyrosine/metabolism MH - src Homology Domains/physiology EDAT- 1999/09/16 00:00 MHDA- 1999/09/16 00:01 CRDT- 1999/09/16 00:00 PHST- 1999/09/16 00:00 [pubmed] PHST- 1999/09/16 00:01 [medline] PHST- 1999/09/16 00:00 [entrez] AID - S0014-4886(99)97148-0 [pii] AID - 10.1006/exnr.1999.7148 [doi] PST - ppublish SO - Exp Neurol. 1999 Sep;159(1):297-308. doi: 10.1006/exnr.1999.7148.