Protein Synthesis/Degradation: Protein Degradation – Protease Classes – Kallikrein and Kallikrein-Related Peptidases

Abstract

Plasma and tissue kallikreins were defined by their ability to liberate the vasoactive peptides, kinins, from kininogens. Plasma kallikrein functions in the vascular space and is responsible for the formation of bradykinin. It also participates in the contact phase of blood coagulation. Tissue kallikrein is present in glandular secretions and in the interstitial space. Research in the past 20 years has identified 14 other enzymes, which have homology to tissue kallikrein and, along with it, form a family known as kallikrein-related peptidases. Both plasma kallikrein and the kallikrein-related peptidase family are synthesized in zymogen form, which are activated by limited proteolysis. The kallikrein-related peptidases have diverse functions as regulatory proteases, including catalyzing zymogen activation to form functional cascades, degrading extracellular matrix, contributing to the regulation of cell growth by the release of insulin-like growth factor from complexes with insulin-like growth factor binding proteins, and acting directly on cells via protease-activated receptors. The pleiotropic nature of kallikrein-related peptidase function is suggested to be important in tumor growth and metastasis.