Proprotein convertases

Like all neuropeptides, NT is synthesized as part of a larger precursor that also contains neuromedin N (NN), a 6 amino acid neurotensin-like peptide (Table 1). Pro-NT/NN is processed in the regulated secretory pathway of neuroendocrine cells by prohormone convertases PCI, PC2 and PC5-A that belong to a larger family of proprotein convertases. Due to differential cleavage specificity and tissue distribution of the convertases, pro-NT/NN processing gives rise to approximately a 1 1 and a 5 1 ratio of NT over NN content in the brain and gut, respectively. The peptides are stored in secretory vesicles and released from neuroendocrine cells in a Ca2+-dependent manner. NT and NN actions are terminated by desensitization of the... 

SB 1 Family of endo- and exopeptidases (including proprotein convertases) Asp, His, Ser Parallel /3-sheet... 

Furin (proprotein convertase) [200] furin required for cancer invasiveness hence good chemotherapy target... 

PCSK9, proprotein convertase subtUisin/kexin type 9 PPAR-y, peroxisome-proliferator-activated receptor-y receptor agonists PPG, post-prandial... 

Significantly, the approach of activity profiling for cysteine proteases has established cathepsin L as a new protease pathway for neuropeptide biosynthesis. Together with current knowledge in the field, these data demonstrate the existence of two distinct protease pathways for converting proneuropeptides into active peptide neurotransmitters and hormones. These dual pathways consist of the newly discovered cysteine protease pathway for proneuropeptide processing, which consists of cathepsin L followed by Arg/Lys aminopeptidase (aminopeptidase B), and the previously known proprotein convertase (PC) family of subtilisin-like proteases (15-17) that process proneuropeptides with carboxypeptidase E (Fig. 3). Elucidation of these two protease pathways resulted from the application of the biochemical criteria required for processing proteases. 

Basak A, Koch P, Dupelle M, Pricker LD, Devi LA, Chrdtien M, Seidah NG. Inhibitory specificity and potency of proSAAS-derived peptides toward proprotein convertase 1. J. Biol. Chem. 2001 276 32720-32728. 

Figure 7 Maturation of insulin. Insulin is synthesized as preproinsulin that contains an N-terminal signal sequence. After translocating into the ER, the signal sequence is cleaved off by the signal peptidase and the resulting proinsulin folds into a stable conformation. Three disulfide bonds are formed between cysteine side chains. The connecting sequence (Chain C) is cleaved off in the Golgi by proprotein convertases to form the mature and active insulin molecule, which is then secreted.

Many secreted proteins, which include insulin, TGFpi (transforming growth factor (U), nerve growth factor pi, albumin, Factor IX, insulin receptor, and Notch, also contain a propeptide that is cleaved by proprotein convertases in the Golgi... 

Turpeinen H, Raitoharju E, Oksanen A, Oksala N, Levula M, Lyytikainen LP, Jarvinen O, Creemers JW, Kahonen M, Laaksonen R, Pelto-Huikko M, Lehtimaki T, Pesu M (2011) Proprotein convertases in human atherosclerotic plaques the overexpression of FURIN and its substrate cytokines BAFF and APRIL. Atherosclerosis 219 799-806... 

Seidah NG, Prat A (2007) The proprotein convertases are potential targets in the treatment of dyslipidemia. J Mol Med (Berl) 85 685-696... 

Neoandrographolide (= Andrographolide 0-glucoside) (diterpene) Andrographis paniculata (Acanthaceae) Proprotein convertase (PPC) PPC-1, PPC-7, Furin (a PPC) (54 pM) [107]... 

Chretien, M., Mbikay, M., Caspar, L., and Seidah, N.G. (1995). Proprotein convertases and the pathophysiology of human disease Prospective considerations. Proc. Assoc. Am. Phys. 107 41-66. 

Scopsi L, Gullo M, Rilke F, et al. Proprotein convertases (PCI/ PC3 and PC2) in normal and neoplastic tissues Their use as markers of NE differentiation. J Clin Endocrinol Metab. 1995 80 294-301. 

Proprotein convertase subtilisin-like kexin-type 9 (PCSK9). 565... 

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