The Molecular Biology of the Kallikreins and their Roles in Inflammation

This chapter focuses primarily on the molecular biology of the tissue kallikrein (KLK) gene family. The chapter emphasizes on the differences in gene structure and organization between the plasma and tissue KLK genes and the latter family of genes. Greater appreciation has developed of the varied role of the tissue KLK–kinin system in human (patho)physiology as the molecular biology, and physiology of the tissue KLK gene family of enzymes and other components of this system have been more extensively characterized in the chapter. As relatively little research has been performed specifically on the molecular regulation and expression of tissue KLKs in inflammatory events, the review provided in the chapter describes the current knowledge of the basic molecular biology of this gene family, with both old and new findings that lead to the better understanding of the role of these enzymes in inflammation. The KLKs are a group of serine proteases involved in the posttranslational processing of polypeptide precursors. With respect to the kinin system, they consist primarily of plasma KLK and tissue or glandular KLK. Plasma KLK is encoded by a single gene and bears no sequence or structural relationship to tissue KLK. Plasma prekallikrein is expressed solely in the liver, circulating as a complex with its substrate, high-molecular-weight kininogen (HMWK), before releasing bradykinin (BK) at predetermined sites in the vasculature. Tissue KLK is a member of a large multigene family of enzymes, which are highly conserved in sequence and tertiary structure