Ullrich A, Gray A, Berman C, Dull T J
Nature. 1983 Jun 30;303(5920):821-5. doi: 10.1038/303821a0.
Nerve growth factor (NGF) is thought to have a profound effect on the development and maintenance of sympathetic and embryonic sensory neurones (see refs 1-3 for review). NGF activity isolated from the male mouse submaxillary gland (MSG) consists of three types of subunits, alpha, beta and gamma, which specifically interact to form a 7S, approximately 130,000-molecular weight (Mr) complex. The 7S complex contains two identical 118-amino acid beta-chains, which are solely responsible for the nerve growth-stimulating activity of NGF. While NGF is found in almost all vertebrates, most research has focused on murine NGF, as the mouse male submaxillary gland contains higher levels of this polypeptide than other tissues. Even so, beta-NGF comprises only approximately 0.1% of the protein in this small gland, which has made the study of this polypeptide difficult. The amino acid sequence of the mouse NGF beta-chain has been determined and some information has been obtained regarding the size of a mouse precursor molecule, pro-beta-NGF, but little was known about the structure and relatedness of beta-NGF from other vertebrates. Here we describe the isolation of mouse beta-NGF complementary DNA (cDNA) and present its nucleotide sequence, which predicts a prepro-beta-NGF molecule of Mr 27,000 (27K) and a pro-beta-NGF molecule of Mr 25K. We have used the mouse beta-NGF cDNA clone to isolate the human beta-NGF gene, the coding regions of which are highly homologous to the mouse prepro-beta-NGF nucleotide and amino acid sequences.
神经生长因子(NGF)被认为对交感神经和胚胎感觉神经元的发育与维持具有深远影响(综述见参考文献1 - 3)。从雄性小鼠颌下腺(MSG)分离出的NGF活性由三种亚基组成,即α、β和γ,它们特异性相互作用形成一个7S、分子量约为130,000(Mr)的复合物。该7S复合物包含两条相同的118个氨基酸的β链,它们是NGF神经生长刺激活性的唯一负责者。虽然几乎在所有脊椎动物中都能发现NGF,但大多数研究都集中在鼠源NGF上,因为小鼠雄性颌下腺中这种多肽的含量比其他组织更高。即便如此,β - NGF在这个小腺体中仅占蛋白质的约0.1%,这使得对这种多肽的研究变得困难。小鼠NGFβ链的氨基酸序列已被确定,并且已经获得了一些关于小鼠前体分子pro - β - NGF大小的信息,但对于其他脊椎动物β - NGF的结构和相关性知之甚少。在此,我们描述了小鼠β - NGF互补DNA(cDNA)的分离并给出其核苷酸序列,该序列预测出一个Mr为27,000(27K)的前原β - NGF分子和一个Mr为25K的pro - β - NGF分子。我们已使用小鼠β - NGF cDNA克隆分离出人类β - NGF基因,其编码区与小鼠前原β - NGF核苷酸和氨基酸序列高度同源。