Salvas Alexandre, Benjannet Suzanne, Reudelhuber Timothy L, Chrétien Michel, Seidah Nabil G
Biochemical Neuroendocrinology Laboratory, Clinical Research Institute of Montreal, QC, Canada.
FEBS Lett. 2005 Oct 24;579(25):5621-5. doi: 10.1016/j.febslet.2005.09.029. Epub 2005 Sep 28.
Processing of precursor proteins by the proprotein convertases is thought to occur mainly in the trans-Golgi network or post-Golgi compartments. Such cleavage is inhibited by the prosegment of the convertases. During our studies of the use of the inhibitory prosegment of PC1, we noticed that a construct containing the prosegment fused to the C-terminal secretory granule sorting domain was cleaved in the endoplasmic reticulum (ER) at a pair of basic residues, best recognized by furin and PC7. This was further confirmed when this construct was fused at the C-terminus with a KDEL ER-retention signal. This suggests that the convertases could cleave some substrates within the ER, possibly by displacing the inhibitory prosegment associated with them.
前体蛋白转化酶对前体蛋白的加工被认为主要发生在反式高尔基体网络或高尔基体后区室中。这种切割会被转化酶的前肽段所抑制。在我们对PC1抑制性前肽段的应用研究过程中，我们注意到一个构建体，其包含与C端分泌颗粒分选结构域融合的前肽段，该构建体在内质网（ER）中一对碱性残基处被切割，这种切割最易被弗林蛋白酶和PC7识别。当该构建体在C端与KDEL内质网滞留信号融合时，这一点得到了进一步证实。这表明转化酶可能在内质网内切割某些底物，可能是通过取代与其相关的抑制性前肽段来实现的。
