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Volume 272, Number 20, Issue of May 16, 1997 pp. 13019-13025
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

TrkB Variants with Deletions in the Leucine-rich Motifs of the Extracellular Domain

(Received for publication, October 22, 1996, and in revised form, March 5, 1997)

Natalia Ninkina , Marina Grashchuck , Vladimir L. Buchman and Alun M. Davies

From the School of Biological and Medical Sciences, University of St. Andrews, St. Andrews, Fife KY16 9AJ, Scotland

We have isolated two novel variants involving the extracellular domain of TrkB from developing sensory neurons. These variants are generated by alternative splicing and lack two or all three of the leucine-rich motifs. Each of these variants is expressed as isoforms that possess or lack the intracellular tyrosine kinase domain. Fibroblast cell lines stably expressing these variants do not bind any of the TrkB ligands (brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5) and neither survive nor undergo morphological transformation in response to neurotrophins. These results demonstrate that the leucine-rich motifs in TrkB are essential for ligand binding and signaling and indicate that the extracellular immunoglobulin-like domains alone are insufficient to confer neurotrophin binding to TrkB.


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Copyright © 1997 by the American Society for Biochemistry and Molecular Biology.