Strohmaier C, Carter B D, Urfer R, Barde Y A, Dechant G
Max-Planck-Institute for Psychiatry, Department of Neurobiochemistry, Planegg-Martinsreid, Germany.
EMBO J. 1996 Jul 1;15(13):3332-7.
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.
TrkB基因编码一种受体酪氨酸激酶，它对于外周神经系统的发育至关重要。该受体可被三种不同的神经营养因子激活：脑源性神经营养因子（BDNF）、神经营养因子-4/5（NT-4/5）和神经营养因子-3（NT-3）。已发现TrkB的细胞外结构域由10个外显子编码，这些外显子对应于先前基于蛋白质序列比较确定的受体亚结构域。在TrkB基因的一种新型酪氨酸激酶转录本中，外显子9被跳过，该转录本被命名为ctrkB-Short（ctrkB-S）。虽然先前描述的TrkB受体ctrkB-Long（ctrkB-L）和TrkB-S受体被BDNF激活的方式相似，但通过配体结合、配体诱导的自磷酸化以及p21ras的配体依赖性激活检测发现，TrkB-S与NT-4/5和NT-3的相互作用较弱。通过在NT-3中进行单个氨基酸替换（D15A），可恢复NT-3对ctrkB-S的有效激活。在胚胎神经元中检测到了ctrkB-L和ctrkB-S转录本。
