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编码小鼠神经生长因子前体的cDNA的分离及核苷酸序列

Isolation and nucleotide sequence of a cDNA encoding the precursor of mouse nerve growth factor.

作者信息

Scott J, Selby M, Urdea M, Quiroga M, Bell G I, Rutter W J

出版信息

Nature. 1983 Apr 7;302(5908):538-40. doi: 10.1038/302538a0.

DOI:10.1038/302538a0
PMID:6336309
Abstract

Nerve growth factor (NGF) is a polypeptide that enhances survival, nerve fibre outgrowth and neurotransmitter biosynthesis in sympathetic and sensory neurones. Administration of antibodies against NGF to developing animals leads to atrophy of the sympathetic system. NGF is not normally detectable in innervated tissues but ablation of the innervating neurones leads to the production of measurable NGF in the target tissue. After transplantation of the denervated tissue, reinnervation occurs, then NGF decreases to undetectable levels. Thus NGF seems to act as a neurotrophic messenger and its level is regulated by innervating neurones. Because of the minute levels present it is very difficult to study NGF biosynthesis in innervated tissue. However, NGF can be isolated from male mouse submaxillary glands, where it exists in inexplicably high levels. Its amino acid sequence has been determined, and the synthesis of NGF and its larger precursors has been demonstrated in cultured submaxillary glands. We report here the nucleotide sequence of a submaxillary cDNA encoding the mouse NGF precursor (preproNGF). In contrast to previous suppositions the NGF moiety is situated near the carboxyterminus of the polyprotein precursor. It is flanked at the amino-terminus by 187 amino acids which may be cleaved at dibasic residues to generate three peptides; there are only two additional amino acids at the carboxy-terminus.

摘要

神经生长因子(NGF)是一种多肽,可增强交感神经和感觉神经元的存活、神经纤维生长及神经递质生物合成。给发育中的动物注射抗NGF抗体可导致交感神经系统萎缩。在受神经支配的组织中通常检测不到NGF,但切断支配神经元会导致靶组织中产生可测量的NGF。去神经组织移植后,会发生重新神经支配,然后NGF降至无法检测的水平。因此,NGF似乎起着神经营养信使的作用,其水平受支配神经元调节。由于其含量极低,很难在受神经支配的组织中研究NGF的生物合成。然而,NGF可从雄性小鼠颌下腺中分离出来,其在颌下腺中的含量高得令人费解。其氨基酸序列已被确定,并且在培养的颌下腺中已证明了NGF及其更大前体的合成。我们在此报告编码小鼠NGF前体(前原NGF)的颌下腺cDNA的核苷酸序列。与先前的推测相反,NGF部分位于多蛋白前体的羧基末端附近。其氨基末端侧翼有187个氨基酸,这些氨基酸可能在双碱性残基处被切割以产生三种肽;羧基末端仅还有另外两个氨基酸。

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