HUMAN BETA-NERVE GROWTH-FACTOR GENE SEQUENCE HIGHLY HOMOLOGOUS TO THAT OF MOUSE

HUMAN BETA-NERVE GROWTH-FACTOR GENE SEQUENCE HIGHLY HOMOLOGOUS TO THAT OF MOUSE
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DOI:
10.1038/303821a0
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发表时间:
1983-01-01
期刊:
影响因子:
64.8
通讯作者:
DULL, TJ
DULL, TJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
ULLRICH, A;GRAY, A;DULL, TJ

文献摘要

被引文献

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神经生长因子(NGF)被认为对交感和胚胎感觉神经元的发育和维持有深远的影响(见文献1-3)。从雄性小鼠颌下腺分离的神经生长因子活性由α,β和γ三种亚基组成,它们特异性地相互作用形成一个7S,∼130,000分子量(MR)的复合体。7S复合体包含两个相同的118个氨基酸的β链,它们单独负责神经生长因子的神经生长刺激活性。虽然NGF在几乎所有脊椎动物中都有发现,但大多数研究都集中在小鼠的NGF上,因为小鼠的雄性颌下腺含有比其他组织更高水平的这种多肽。尽管如此,β-NGF只占这个小腺体蛋白质的0.1%,这使得对这种多肽的研究变得困难。已经测定了小鼠神经生长因子β链的氨基酸序列,并获得了一些关于小鼠前体分子6-β-NGF的大小的信息,但对其他脊椎动物的β-NGF的结构和相关性知之甚少。在这里,我们描述了小鼠β-NGF互补基因的分离,并给出了它的核苷酸序列,它预测了一个Mr 27000(27K)的前β-NGF分子和一个Mr 25K的前β-NGF分子。我们用小鼠β-NGF基因克隆克隆了人β-NGF基因,该基因的编码区与小鼠前β-NGF核苷酸和氨基酸序列高度同源。
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,α,βandγ, which specifically interact to form a 7S, ∼130,000-molecular weight (Mr) complex. The 7S complex contains two identical 118-amino acidβ-chains, which are solely responsible for the nerve growth-stimulating activity of NGF. While NGF is found in almost all vertebrates4, most research has focused on murine NGF, as the mouse male submaxillary gland contains higher levels of this polypeptide than other tissues4. Even so,β-NGF comprises only ∼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 NGFβ-chain has been determined5and some information has been obtained regarding the size of a mouse precursor molecule6, pro-β-NGF, but little was known about the structure and relatedness ofβ-NGF from other vertebrates. Here we describe the isolation of mouseβ-NGF complementary DNA (cDNA) and present its nucleotide sequence, which predicts a prepro-β-NGF molecule ofMr27,000 (27K) and a pro-β-NGF molecule ofMr25K. We have used the mouseβ-NGF cDNA clone to isolate the humanβ-NGF gene, the coding regions of which are highly homologous to the mouse prepro-β-NGF nucleotide and amino acid sequences.