Molecular biology of the angiotensinogen and kininogen genes.

In order to investigate the structures and expressions of the angiotensinogen and kininogen genes, we have isolated cDNA and genomic clones and characterized their structures. The following results were obtained. (a) The primary structures of rat and human angiotensinogens and bovine, human, and rat kininogens were determined, and they exhibit characteristic features. (b) Angiotensinogen and alpha 1-antitrypsin are related in not only protein structures but also gene organizations. (c) Angiotensinogen mRNA is synthesized not only in the liver but also in the brain, kidney, lung, adrenal gland, and ovary. (d) Angiotensinogen mRNA markedly increased in the liver but not in the brain after induction of acute inflammation. (e) Low molecular weight (LMW) and high molecular weight (HMW) kininogen mRNAs are generated from a single gene by alternative RNA processing events. (f) At least four types of kininogen mRNAs exist in rat liver. Two of them are LMW and HMW kininogen mRNAs, while the other two encode additional forms of kininogens (T-kininogens). (g) Two T-kininogen mRNAs but not LMW and HMW kininogen mRNAs dramatically increased after induction of acute inflammation, and T-kininogen turned out to be identical to alpha 1-major acute phase protein. (h) Kininogens have multifunctional domains; an amino-terminal domain for cystein proteinase inhibitor, a bradykinin moiety, and in the case of HMW kininogen a carboxyl-terminal domain for a cofactor of blood coagulation.