Kallikrein multigene families and the regulation of their expression

Tissue kallikreins are a group of closely related serine proteinases that are represented by multigene families in mice and rats. The existence of similar, large, kallikrein-like gene families in other mammalian species is currently a matter of dispute. We have surveyed a number of vertebrate species using genomic DNA Southern blotting and screened a human genomic library with a monkey kallikrein cDNA probe. The hybridization patterns of the genomic Southern blots and the characterization of 19 independent human clones using restriction analysis and Southern blotting indicate that other mammalian species may have multiple kallikrein-like genes as well. The regulatory mechanisms that govern the expression, activity, and bioavailability of tissue kallikreins are likewise complex. At the level of transcription, hormones, dietary factors, and tissue-specific factors are known to affect the expression of tissue kallikrein genes. At the posttranslational level, kallikrein activity and bioavailability are regulated by enzymatic activation, circulating autoantibodies, and binding proteins. We have demonstrated the presence of kallikrein-binding proteins in humans and rats, and, furthermore, we have shown reduced levels of this binding protein in a hypertensive rat model.