Characterization and Substrate Specificities of Various Mouse Kallikreins

Abstract

Kallikrein gene family in mouse consists of 25 gene members.Only few members of this family have been characterized.These include epidermal growth factor binding proteins A, -B, -C, γ-renin, α- and γ- nerve growth factors (α- and γ-NGF’s) and prorenin converting enzyme.These proteins show specificity towards various growth factors and enzymes.We have carried out the characterization of mK11, a product of clone mKlk-11. This protein was present at higher levels in the mice genetically selected for high blood pressure.However, the protein was not detected in the mice selected for low blood pressure. The substrate specificity of this protein was tested on tetradecapeptide (TDP, a renin substrate) and β-lactoglobulin (β-lg). The protein shows specificity toward Tyr-Ile (4–5) bond in TDP and Tyr-Ser (20–21) and Arg-Val (40–41) bonds in β-lg. Another member of the kallikrein family, γ-NGF was found to cleave the Phe-His (8–9) bond in TDP.The cleavage specificity of these proteins raises the possibility of the involvement of these proteins in the processing of angiotensin-II (AT-II). Furthermore, these proteins may play a role in the regulation of local blood pressure/flow. The characterization of these kallikrein family members and determination of their substrate specificities is presented.