Processing of the native nerve growth factor precursor to form biologically active nerve growth factor.
In the mouse submaxillary gland beta nerve growth factor (beta-NGF) forms a complex with two members of the kallikrein family of serine proteases, termed the alpha- and gamma-subunits of NGF. We demonstrate that the beta-NGF precursor produced in mammalian cells via a recombinant vaccinia virus can be cleaved by stoichiometric quantities of the gamma-subunit to produce beta-NGF. Trypsin in catalytic quantities also produces native beta-NGF. Proper cleavage depends critically on the conformation of the precursor. beta-NGF has at least 10-fold more biological activity than its precursor.
Edwards
R H
RH
Departments of Biochemistry and Biophysics, University of California, San Francisco 94143.
Selby
M J
MJ
Garcia
P D
PD
Rutter
W J
WJ
D000818:Animals; D004247:DNA / Q000235:genetics; D051379:Mice; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics*; D014176:Protein Biosynthesis; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics*; D011499:Protein Processing, Post-Translational; D013363:Submandibular Gland / Q000378:metabolism; D014158:Transcription, Genetic
D009414:Nerve Growth Factors; D011498:Protein Precursors; C044242:nerve growth factor, beta subunit precursor; D004247:DNA