title: Two conserved domains in the NGF propeptide are necessary and sufficient for the biosynthesis of correctly processed and biologically active NGF.
abstract: The three members of the neurotrophin family (NGF, BDNF and NT-3) are synthesized as large precursor proteins which undergo proteolytic processing to yield biologically active, mature neurotrophic factors. We have used in vitro mutagenesis to examine the pro-region in the NGF precursor protein as a first step towards a general understanding of the role of propeptides in the biosynthesis of neurotrophins. Our results demonstrate that only two small domains within the NGF propeptide are required for the expression and secretion of properly processed and biologically active, recombinant mouse NGF in COS-7 cells. Domain I plays an important role in the expression of active NGF while domain II is involved in proteolytic processing. Both domains are partially conserved between the propeptides of NGF proteins isolated from different species as well as BDNF and NT-3.
authors.affiliation: Department of Neurobiology, Stanford University School of Medicine, CA 94305-5401.
authors.forename: U
authors.initials: U
authors.lastname: Suter
authors.forename: J V
authors.initials: JV
authors.lastname: Heymach
authors.forename: E M
authors.initials: EM
authors.lastname: Shooter
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002872:Chromosome Deletion; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D006868:Hydrolysis; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000378:metabolism; D011498:Protein Precursors / Q000096:biosynthesis / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals / Q000378:metabolism
chemical_list: D009414:Nerve Growth Factors; D011498:Protein Precursors; D021382:Protein Sorting Signals; D004247:DNA