Kallikrein-related peptidase 14 is the second KLK protease targeted by the serpin vaspin.

Kallikrein-related peptidases KLK5, KLK7 and KLK14 are important proteases in skin desquamation and aberrant KLK activity is associated with inflammatory skin diseases such as Netherton syndrome but also with various serious forms of cancer. Previously, we have identified KLK7 as the first protease target of vaspin (Serpin A12). Here, we report KLK14 as a second KLK protease to be inhibited by vaspin.

Glycosylation of human vaspin (SERPINA12) and its impact on serpin activity, heparin binding and thermal stability.

Vaspin is a glycoprotein with three predicted glycosylation sites at asparagine residues located in proximity to the reactive center loop and close to domains that play important roles in conformational changes underlying serpin function. In this study, we have investigated the glycosylation of human vaspin and its effects on biochemical properties relevant to vaspin function. We show that vaspin is modified at all three sites and biochemical data demonstrate that glycosylation does not hinder inhibition of the target protease kallikrein 7.

Basic Residues of β-Sheet A Contribute to Heparin Binding and Activation of Vaspin (Serpin A12).

Many members of the serine protease inhibitor (serpin) family are activated by glycosaminoglycans (GAGs). Visceral adipose tissue-derived serpin (vaspin), serpin A12 of the serpin family, and its target protease kallikrein 7 (KLK7) are heparin-binding proteins, and inhibition of KLK7 by vaspin is accelerated by heparin. However, the nature of GAG binding to vaspin is not known.

The amyloid precursor protein shows a pH-dependent conformational switch in its E1 domain.

The amyloid precursor protein (APP) and its proteolytic cleavage product Aβ are widely believed to be central to the etiology of Alzheimer's disease (AD). APP and its family members are also essential for proper neuronal development and homeostasis. APP is located at the cell surface and within intracellular compartments, cellular regions that exhibit different pH values.