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Human kallikrein-related peptidases (KLKs), including the well-known prostate cancer biomarker, prostate-specific antigen (PSA-KLK3), along with 14 other serine proteinase KLK family members are now known to regulate cells by cleaving and activating members of the G-protein-coupled proteinase-activated receptor (PAR) family. This hormone-like signaling action of the KLKs has provided a new perspective for understanding the biological roles that KLKs may play in normal and pathophysiological settings. This overview summarizes the circumstances leading up to the discovery of this action of the KLKs and provides an overview of the diverse impact on tissue function that may result from KLK-triggered PAR activation.

KLKs and their hormone-like signaling actions: a new life for the PSA-KLK family