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

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.

Synthesis and partial maturation of the α‐ and γ‐subunits of the mouse submaxillary gland nerve growth factor in Xenopus laevis oocytes

“…The 3 subunits undergo posttranslational modifications. The mGF monomer is thought to derive from a precursor of n/r about 3ClooO [6]. The yNGF is possibly involved in its maturation [7].…”

Cellular processing of the neurotrophin precursors of NT3 and BDNF by the mammalian proprotein convertases

“…Levi-Montalcini and coworkers discovered nerve growth factor (NGF), the first member of the family, over forty years ago (for review see [1]). Since the cDNA structure coding for the precursor of NGF (proNGF) was reported [2], four other members of the family have been identified and their cDNAs cloned: brain-derived neurotrophic factor (BDNF) [3], neurotrophin-3 (NT3) [4,5], neurotrophin-4/5 (NT-4/5) [6] and neurotrophin-6 (NT-6) [7]. Sequence data predict that all neurotrophins are generated from 31 35 kDa precursors that contain at their N-termini, hydrophobic signal peptides followed by proregions containing sequences of contiguous basic amino acids.…”

Gene transfer to the central nervous system by transplantation of cerebral endothelial cells

“…NGF cDNA 36 at the position 897-944 (probe synthesized by R&D Systems Europe, Oxon, UK). Control experiAll animal procedures were in strict accordance with NIH guidelines and French ethics committee.…”