Kininogens

Literature References: Precursor molecules of the vasoactive kinins. Also serve as endogenous cysteine proteinase inhibitors known as type 3 cystatins and are essential cofactors for the contact activation of blood clotting. Single chain glycoproteins synthesized by hepatocytes and secreted into plasma. Three forms have been identified in mammals: H-kininogen (HK) having a molecular mass of 88-115 kDa, L-kininogen (LK) with molecular mass of 50-68 kDa, and T-kininogen, mol wt 68 kDa, which has been found only in rats. Structures consist of an amino-terminal heavy chain portion linked to a carboxy terminal light chain by the kinin segment which is released by kallikrein, q.v. The heavy chain contains 3 tandemly repeated domains that are structurally homologous to the type-2 cystatins, q.v. The HK light chain contains 2 additional domains that are responsible for the procoagulant activity. Purification from bovine serum: E. Habermann et al., Z. Phys. Chem. 332, 121 (1963); eidem, Biochem. Z. 337, 440 (1963). Isoln of 2 forms from human plasma: F. M. Habal et al., Biochem. Pharmacol. 23, 2291 (1974). Review of purification methods and structure: H. Kato et al., Methods Enzymol. 80, Part C, 172-199 (1981). Identity with a-cysteine proteinase inhibitors: W. Müller-Esterl et al., FEBS Lett. 182, 310 (1985). Review of structure and function: R. A. DeLa Cadena, R. W. Colman, Trends Pharmacol. Sci. 12, 272-275 (1991); of biological role: K. D. Bhoola et al., Pharmacol. Rev. 44, 1-80 (1992); C. Blais, Jr. et al., Peptides 21, 1903-1940 (2000).