PMID- 1649703 OWN - NLM STAT- MEDLINE DCOM- 19910827 LR - 20190705 IS - 0092-8674 (Print) IS - 0092-8674 (Linking) VI - 66 IP - 2 DP - 1991 Jul 26 TI - TrkB mediates BDNF/NT-3-dependent survival and proliferation in fibroblasts lacking the low affinity NGF receptor. PG - 405-13 AB - The neurotrophins (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin-3 [NT-3], and neurotrophin-4 [NT-4] ) have been defined by their ability to support neuronal survival. These factors utilize the Trk family of receptor tyrosine kinases, perhaps in conjunction with a second component known as the low affinity NGF receptor (LNGFR). Here we demonstrate that TrkB mediates survival and proliferation in response to both BDNF and NT-3 when expressed in a particular strain of NIH 3T3 fibroblasts, with BDNF the more potent ligand. Furthermore, the BDNF dose dependency displayed by these TrkB-expressing fibroblasts is similar to that required to support the survival of primary neurons. The LNGFR is not expressed in our fibroblast system, implying that this receptor is not essential for responses to physiological concentrations of the neurotrophins. We discuss our findings in the context of neurotrophin signaling pathways and mechanisms of neuronal cell death. FAU - Glass, D J AU - Glass DJ AD - Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591. FAU - Nye, S H AU - Nye SH FAU - Hantzopoulos, P AU - Hantzopoulos P FAU - Macchi, M J AU - Macchi MJ FAU - Squinto, S P AU - Squinto SP FAU - Goldfarb, M AU - Goldfarb M FAU - Yancopoulos, G D AU - Yancopoulos GD LA - eng PT - Journal Article PL - United States TA - Cell JT - Cell JID - 0413066 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Membrane Glycoproteins) RN - 0 (Nerve Growth Factors) RN - 0 (Nerve Tissue Proteins) RN - 0 (Neurotrophin 3) RN - 0 (Receptors, Cell Surface) RN - 0 (Receptors, Nerve Growth Factor) RN - 0 (Recombinant Proteins) RN - EC 2.7.10.1 (Ntrk2 protein, mouse) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor MH - Cell Division/drug effects MH - Cell Line MH - Cell Survival/drug effects MH - DNA Replication/drug effects MH - Fibroblasts/cytology/drug effects MH - Membrane Glycoproteins/*metabolism MH - Mice MH - Nerve Growth Factors/*pharmacology MH - Nerve Tissue Proteins/*pharmacology MH - Neurotrophin 3 MH - Protein-Tyrosine Kinases/*metabolism MH - Receptor, trkB MH - Receptors, Cell Surface/physiology MH - Receptors, Nerve Growth Factor MH - Recombinant Proteins/pharmacology MH - Transfection EDAT- 1991/07/26 00:00 MHDA- 1991/07/26 00:01 CRDT- 1991/07/26 00:00 PHST- 1991/07/26 00:00 [pubmed] PHST- 1991/07/26 00:01 [medline] PHST- 1991/07/26 00:00 [entrez] AID - 0092-8674(91)90629-D [pii] AID - 10.1016/0092-8674(91)90629-d [doi] PST - ppublish SO - Cell. 1991 Jul 26;66(2):405-13. doi: 10.1016/0092-8674(91)90629-d.