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Signal Transduction Mediated by the Truncated trkB Receptor Isoforms, trkB.T1 and trkB.T2
- Source :
- The Journal of Neuroscience. 17:2683-2690
- Publication Year :
- 1997
- Publisher :
- Society for Neuroscience, 1997.
-
Abstract
- The trkB family of transmembrane proteins serves as receptors for BDNF and NT-4/5. The family is composed of a tyrosine kinase-containing isoform as well as several alternatively spliced “truncated receptors” with identical extracellular ligand-binding domains but very small intracellular domains. The two best-characterized truncated trkB receptors, designated as trkB.T1 and trkB.T2, contain intracellular domains of only 23 and 21 amino acids, respectively. Although it is known that the tyrosine kinase isoform (trkB.FL) is capable of initiating BDNF and NT-4/5-induced signal transduction, the functional role or roles of the truncated receptors remain enigmatic. At the same time, the potential importance of the truncated receptors in the development, maintenance, and regeneration of the nervous system has been highlighted by recent developmental and injury paradigm investigations. Here we have used trkB cDNA transfected cell lines to demonstrate that both trkB.T1 and trkB.T2 are capable of mediating BDNF-induced signal transduction. More specifically, BDNF activation of either trkB.T1 or trkB.T2 increases the rate of acidic metabolite release from the cell, a common physiological consequence of many signaling pathways. Further, these trkB.T1- and trkB.T2-mediated changes occur with kinetics distinct from changes mediated by trkB.FL, suggesting the participation of at least some unique rate-limiting component or components. Mutational analysis demonstrates that the isoform-specific sequences within the intracellular domains of each receptor are essential for signaling capability. Finally, inhibitor studies suggest that kinases are likely to be involved in the trkB.T1 and trkB.T2 signaling pathways.
- Subjects :
- Carbazoles
Receptors, Nerve Growth Factor
Tropomyosin receptor kinase B
Transfection
Polymerase Chain Reaction
Protein Structure, Secondary
Receptor tyrosine kinase
Cell Line
Indole Alkaloids
Mice
L Cells
Cerebellum
Animals
Humans
Nerve Growth Factors
Enzyme Inhibitors
Tyrosine
Receptor
Receptor, Ciliary Neurotrophic Factor
Sequence Deletion
biology
Brain-Derived Neurotrophic Factor
musculoskeletal, neural, and ocular physiology
General Neuroscience
Articles
Protein-Tyrosine Kinases
Staurosporine
Recombinant Proteins
Rats
Cell biology
Alternative Splicing
nervous system
Biochemistry
embryonic structures
Mutagenesis, Site-Directed
biology.protein
Signal transduction
Proto-Oncogene Proteins c-fos
Tyrosine kinase
Intracellular
Signal Transduction
Neurotrophin
Subjects
Details
- ISSN :
- 15292401 and 02706474
- Volume :
- 17
- Database :
- OpenAIRE
- Journal :
- The Journal of Neuroscience
- Accession number :
- edsair.doi.dedup.....742fe3c7eef17be111f9042fb13659e1
- Full Text :
- https://doi.org/10.1523/jneurosci.17-08-02683.1997