Evidence for proprotein convertase activity in the endoplasmic reticulum/early Golgi.
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.
Salvas
Alexandre
A
Biochemical Neuroendocrinology Laboratory, Clinical Research Institute of Montreal, QC, Canada.
Benjannet
Suzanne
S
Reudelhuber
Timothy L
TL
Chrétien
Michel
M
Seidah
Nabil G
NG
D000595:Amino Acid Sequence; D000818:Animals; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000378:metabolism; D045683:Furin / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D045664:Proprotein Convertase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D022142:Secretory Vesicles / Q000201:enzymology; D013381:Subtilisins / Q000378:metabolism; D021601:trans-Golgi Network / Q000201:enzymology*
D004791:Enzyme Inhibitors; D011993:Recombinant Fusion Proteins; C099101:PCSK7 protein, human; D013381:Subtilisins; D045683:Furin; D045664:Proprotein Convertase 1