An immunoglobulin-like domain determines the specificity of neurotrophin receptors
| Autor: | David L. Shelton, Roman Urfer, Leonard G. Presta, Luis F. Parada, Pantelis Tsoulfas, Lori Y. O'Connell |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Glycosylation
animal structures Recombinant Fusion Proteins Molecular Sequence Data Immunoglobulins Nerve Tissue Proteins Receptors Nerve Growth Factor Neurotrophin-3 Tropomyosin receptor kinase B Tropomyosin receptor kinase A Binding Competitive General Biochemistry Genetics and Molecular Biology Mice Neurotrophin 3 Animals Humans Low-affinity nerve growth factor receptor Amino Acid Sequence Nerve Growth Factors Phosphorylation Molecular Biology Sequence Deletion Brain-derived neurotrophic factor Base Sequence General Immunology and Microbiology biology Brain-Derived Neurotrophic Factor General Neuroscience 3T3 Cells Molecular biology Rats Molecular Weight nervous system Trk receptor biology.protein Research Article Binding domain Neurotrophin |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 0261-4189 |
| DOI: | 10.1002/j.1460-2075.1995.tb07279.x |
| Popis: | The neurotrophins influence survival and maintenance of vertebrate neurons in the embryonic, early post-natal and post-developmental stages of the nervous system. Binding of neurotrophins to receptors encoded by the gene family trk initiates signal transduction into the cell. trkA interacts preferably with nerve growth factor (NGF), trkB with brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5) and trkC with neurotrophin-3 (NT-3). By constructing 17 different chimeras and domain deletions of the human trk receptors and analyzing their binding affinities to the neurotrophins we have shown that an immunoglobulin-like domain located adjacent to the transmembrane domain is the structural element that determines the interaction of neurotrophins with their receptors. Chimeras of trkC where this domain was exchanged for the homologous sequences from trkB or trkA gained high affinity binding to BDNF or NGF respectively, while deletion of this domain in trkC or trkA abolished binding to NT-3 or NGF respectively. This domain alone retained affinities to neurotrophins similar to the full-length receptors and when expressed on NIH 3T3 cells in fusion with the kinase domain showed neurotrophin-dependent activation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|