Ibáñez C F, Ebendal T, Persson H
Department of Medical Chemistry, Karolinska Institute, Stockholm, Sweden.
EMBO J. 1991 Aug;10(8):2105-10. doi: 10.1002/j.1460-2075.1991.tb07743.x.
Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are two members of a family of neurotrophic factors which show both overlapping and distinct neurotrophic activities. Using site-directed mutagenesis, chimeric molecules were constructed where different combinations of sequences from BDNF replaced the corresponding sequences in NGF. The resulting molecules were transiently expressed in COS cells and conditioned media containing the chimeric proteins were assayed for biological activity in explanted chick sympathetic, spinal and nodose ganglia. Our results show that the biological specificities of the two proteins are obtained by specific combinations of a set of sequences that differ between the two molecules. Some of these combinations allowed us to engineer molecules which display multiple neurotrophic activities recruited from both the NGF and BDNF proteins.
神经生长因子（NGF）和脑源性神经营养因子（BDNF）是神经营养因子家族的两个成员，它们表现出重叠和独特的神经营养活性。利用定点诱变技术构建了嵌合分子，其中BDNF的不同序列组合取代了NGF中的相应序列。将所得分子在COS细胞中瞬时表达，并检测含有嵌合蛋白的条件培养基在外植的鸡交感神经节、脊髓神经节和结状神经节中的生物活性。我们的结果表明，这两种蛋白质的生物学特异性是由两个分子之间不同的一组序列的特定组合获得的。其中一些组合使我们能够设计出具有从NGF和BDNF蛋白募集的多种神经营养活性的分子。
