PMID- 8174548 OWN - NLM STAT- MEDLINE DCOM- 19940609 LR - 20190620 IS - 0014-2956 (Print) IS - 0014-2956 (Linking) VI - 221 IP - 2 DP - 1994 Apr 15 TI - Purification and characterisation of a brain-derived neurotrophic factor/neurotrophin-3 (BDNF/NT-3) heterodimer. PG - 677-85 AB - The neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) are known to exist in solution as non-covalently linked homodimeric proteins. The recent elucidation of the crystal structure of the NGF homodimer, as well as the conservation of structural motifs in the neurotrophins, raised the possibility that neurotrophin heterodimers might also occur. The formation of BDNF/NT-3 heterodimers was explored using a vaccinia virus expression system. Upon co-infection of cells with viruses expressing BDNF and NT-3, we could identify a BDNF/NT-3 heterodimer as a biosynthetic product and separate it from the BDNF and NT-3 homodimers. We could also show that the BDNF/NT-3 heterodimers can be formed irrespective of wild-type or exchanged prosequences, indicating that prosequence specificity does not influence dimer formation. In all neuronal survival assays that were used, the BDNF/NT-3 heterodimer was shown to be 10-fold less active compared with a mixture of BDNF and NT-3 homodimers. This lower specific activity was also measured in a neuronal population co-expressing receptors for BDNF and NT-3. The low biological activity of the heterodimer observed with neurons was not paralleled by a reduced ability of the heterodimer to interact with trkB or trkC receptors, as assessed by the induction of tyrosine phosphorylation of these receptors expressed by fibroblast cell lines. FAU - Jungbluth, S AU - Jungbluth S AD - Max-Planck Institute for Psychiatry, Department of Neurobiochemistry, Martinsried, Germany. FAU - Bailey, K AU - Bailey K FAU - Barde, Y A AU - Barde YA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Eur J Biochem JT - European journal of biochemistry JID - 0107600 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Nerve Growth Factors) RN - 0 (Nerve Tissue Proteins) RN - 0 (Neurotrophin 3) RN - 0 (Polymers) RN - 0 (Receptor, Ciliary Neurotrophic Factor) RN - 0 (Receptors, Growth Factor) RN - 0 (Recombinant Fusion Proteins) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (Receptor, trkC) SB - IM MH - Amino Acid Sequence MH - Animals MH - Base Sequence MH - Blotting, Western MH - Brain-Derived Neurotrophic Factor MH - Cell Line MH - Cell Survival/drug effects MH - Chick Embryo MH - Mice MH - Molecular Sequence Data MH - Mutation MH - Nerve Growth Factors/*chemistry/isolation & purification/metabolism MH - Nerve Tissue Proteins/*chemistry/isolation & purification/metabolism MH - Neurons/cytology/drug effects MH - Neurotrophin 3 MH - Polymers MH - Rabbits MH - Receptor Protein-Tyrosine Kinases/metabolism MH - Receptor, Ciliary Neurotrophic Factor MH - Receptor, trkC MH - Receptors, Growth Factor/metabolism MH - Recombinant Fusion Proteins/biosynthesis MH - Vaccinia virus/genetics/metabolism EDAT- 1994/04/15 00:00 MHDA- 1994/04/15 00:01 CRDT- 1994/04/15 00:00 PHST- 1994/04/15 00:00 [pubmed] PHST- 1994/04/15 00:01 [medline] PHST- 1994/04/15 00:00 [entrez] AID - 10.1111/j.1432-1033.1994.tb18780.x [doi] PST - ppublish SO - Eur J Biochem. 1994 Apr 15;221(2):677-85. doi: 10.1111/j.1432-1033.1994.tb18780.x.