Processing of nerve growth factor: the role of basic amino acid clusters in the pro-region.
Neurotrophins are synthesized first as precursors called pro-neurotrophins, and their propeptides are then proteolytically removed to form mature neurotrophins. However, a significant proportion of total neurotrophins has been shown to be secreted as pro-neurotrophins. Furthermore, pro- and mature neurotrophins have been shown to elicit opposite effects on cell survival. Thus, the processing step of neurotrophins is very important. In order to understand the mechanism of neurotrophin processing, we focused on the two basic amino acid clusters in the pro-region of nerve growth factor (NGF). Various NGFs mutated at basic amino acids in the pro-region were introduced in COS7 and PC12 cells. The results indicated that these basic amino acid clusters were actually cleaved in the cells by furin, but that their cleavage contributed little to the production of mature NGF. However, one of the two sites was considered to contribute to mature NGF production depending on conditions used.
Mouri
Akihiro
A
Laboratory of Molecular Biology, Gifu Pharmaceutical University, Mitahora-Higashi, Gifu 502-8585, Japan.
Nomoto
Hiroshi
H
Furukawa
Shoei
S
D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D002522:Chlorocebus aethiops; D045683:Furin / Q000378:metabolism; D051379:Mice; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D016716:PC12 Cells; D010957:Plasmids / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D051381:Rats; D014162:Transfection
D000596:Amino Acids; D011498:Protein Precursors; D020932:Nerve Growth Factor; D045683:Furin