Beaufort, Nathalie; Plaza, Karolina; Utzschneider, Daniel; Schwarz, Amelie; Burkhart, Julia M.; Creutzburg, Sabine; Debela, Mekdes; Schmitt, Manfred; Ries, Christian; Magdolen, Viktor
Interdependence of kallikrein-related peptidases in proteolytic networks.
In: Biological Chemistry, Vol. 391, Nr. 5: S. 581-587
Human kallikrein-related peptidases (KLKs) are 15 homologous serine proteases involved in several (patho)physiological processes, including cancer. Secreted as precursors, they are activated upon proteolytic release of a short propeptide. We searched for interconnection of KLKs within extracellular proteolytic networks leading to activation of protease zymogens and found that (i) pro-KLK activation by other KLKs is scarce, with the exception of pro-KLK which is efficiently activated by KLK4 and 5; (ii) pro-KLK4 is activated by matrix metalloproteinase 3; and (iii) trypsin-like KLKs efficiently activate the serine protease urokinase. Our observations provide new insights into the regulation of these important tumor-associated proteases.