A splice variant of the neurotrophin receptor trkB with increased specificity for brain-derived neurotrophic factor.
The trkB gene codes for a receptor tyrosine kinase, which is essential for the development of the peripheral nervous system. This receptor can be activated by three different neurotrophins: BDNF, NT-4/5 and NT-3. The extracellular domain of trkB was found to be encoded in 10 exons corresponding to receptor subdomains previously identified on the basis of protein sequence comparisons. Exon 9 was skipped in a novel tyrosine kinase transcript of the trkB gene, designated ctrkB-Short (ctrkB-S). While the previously described trkB receptor ctrkB-Long (ctrkB-L) and trkB-S receptors were activated similarly by BDNF, trkB-S interacted poorly with NT-4/5 and NT-3 as measured by ligand binding, ligand-induced autophosphorylation and ligand-dependent activation of p21ras. Efficient activation of ctrkB-S by NT-3 was restored by a single amino acid replacement in NT-3 (D15A). Both trkB-L and trkB-S transcripts were detected in embryonic neurons.
Strohmaier
C
C
Max-Planck-Institute for Psychiatry, Department of Neurobiochemistry, Planegg-Martinsreid, Germany.
Carter
B D
BD
Urfer
R
R
Barde
Y A
YA
Dechant
G
G
D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D019208:Brain-Derived Neurotrophic Factor; D002490:Central Nervous System / Q000378:metabolism; D002642:Chick Embryo; D018076:DNA, Complementary; D005091:Exons; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D015689:Oncogene Protein p21(ras) / Q000378:metabolism; D017933:Peripheral Nervous System; D010766:Phosphorylation; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000235:genetics* / Q000378:metabolism*; D013379:Substrate Specificity
D019208:Brain-Derived Neurotrophic Factor; D018076:DNA, Complementary; D008024:Ligands; D009419:Nerve Tissue Proteins; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D015689:Oncogene Protein p21(ras)