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

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Abstract
Nerve growth factor (NGF) is a polypeptide that enhances survival, nerve fibre outgrowth and neurotransmitter biosynthesis in sympathetic and sensory neurones1–3. Administration of antibodies against NGF to developing animals leads to atrophy of the sympathetic system4. NGF is not normally detectable in innervated tissues but ablation of the innervating neurones leads to the production of measurable NGF in the target tissue5. 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 levels6. Its amino acid sequence has been determined7, and the synthesis of NGF and its larger precursors has been demonstrated in cultured submaxillary glands8. We report here the nucleotide sequence of a submaxillary cDNA encoding the mouse NGF precursor (preproNGF). In contrast to previous suppositions8 the NGF moiety is situated near the carboxy-terminus 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.