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Signal Transduction Mediated by the Truncated trkB Receptor Isoforms, trkB.T1 and trkB.T2

Authors :
Victoria Makrides
Angelica Medina-Selby
Beth Hinkle
Monte J. Radeke
Stuart C. Feinstein
Richard Hoang
Pablo Valenzuela
Gregory T. Baxter
Richard C. Kuo
Doris Coit
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.

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