Dj. Pearton et al., Proprotein convertase expression and localization in epidermis: evidence for multiple roles and substrates, EXP DERMATO, 10(3), 2001, pp. 193-203
Specific proteolysis plays an important role in the terminal differentiatio
n of keratinocytes in the epidermis and several types of proteases have bee
n implicated in this process. The proprotein convertases (PCs) are a family
of Ca2+-dependent serine proteases involved in processing and activation o
f several types of substrates. In this study we examined the expression and
some potential substrates of PCs in epidermis, Four PCs are expressed in e
pidermis: furin, PACE4, PC5/6 and PC7/8. Furin is detected in two forms, ei
ther with or without the transmembrane domain, suggesting occurrence of pos
t-translational cleavage to produce a soluble enzyme. In addition the furin
active site has differential accessibility in the granular layer of the ep
idermis relative to the basal layer, whereas antibodies to the transmembran
e domain stain both layers. These findings suggest that furin has access to
different types of substrates in granular cells as opposed to basal cells.
PC7/8, in contrast, is detected throughout the epidermis with antibodies t
o both the transmembrane and active site and no soluble form observed. A pe
ptide PC inhibitor (dec-RVKR-CMK) inhibits cleavage of Notch-1, a receptor
important in cell fate determination that is found throughout the epidermis
. Profilaggrin, found in the granular layer, is specifically cleaved by fur
in and PACE4 in vitro at a site between the amino terminus and the first fi
laggrin repeat. This work suggests that the PCs play multiple roles during
epidermal differentiation.