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The C‐terminal region of the proprotein convertase 1/3 (PC1/3) exerts a bimodal regulation of the enzyme activity in vitro
Author(s) -
Rabah Nadia,
Gauthier Dany,
Dikeakos Jimmy D.,
Reudelhuber Timothy L.,
Lazure Claude
Publication year - 2007
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2007.05883.x
Subject(s) - proprotein convertase , proprotein convertases , in vitro , enzyme , terminal (telecommunication) , pcsk9 , chemistry , biochemistry , microbiology and biotechnology , biology , computer science , ldl receptor , cholesterol , lipoprotein , telecommunications
The proprotein convertase PC1/3 preferentially cleaves its substrates in the dense core secretory granules of endocrine and neuroendocrine cells. Similar to most proteinases synthesized first as zymogens, PC1/3 is synthesized as a larger precursor that undergoes proteolytic processing of its signal peptide and propeptide. The N‐terminally located propeptide has been shown to be essential for folding and self‐inhibition. Furthermore, PC1/3 also possesses a C‐terminal region (CT‐peptide) which, for maximal enzymatic activity, must also be cleaved. To date, its role has been documented through transfection studies in terms of sorting and targeting of PC1/3 and chimeric proteins into secretory granules. In this study, we examined the properties of a 135‐residue purified bacterially produced CT‐peptide on the in vitro enzymatic activity of PC1/3. Depending on the amount of CT‐peptide used, it is shown that the CT‐peptide increases PC1/3 activity at low concentrations (n m ) and decreases it at high concentrations (µ m ), a feature typical of an activator. Furthermore, we show that, contrary to the propeptide, the CT‐peptide is not further cleaved by PC1/3 although it is sensitive to human furin activity. Based on these results, it is proposed that PC1/3, through its various domains, is capable of controlling its enzymatic activity in all regions of the cell that it encounters. This mode of self‐control is unique among members of all proteinases families.