Abstract
The renin-angiotensin and the kallikrein-kinin systems play important physiological roles including regulation of blood pressure and inflammation reactions. Our understanding of the structures, gene organizations and regulations of the enzymes and the peptide precursors in these systems has remarkably increased during the past few years. This article summarizes recent progress in the molecular and genetic studies of renin, angiotensinogen, kallikrein, and kininogens, and discusses some new aspects explored in these areas of research.
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References
Ondetti, M.A. and Cushman, D.W. 1982. Enzymes of the renin-angiotensin system and their inhibitors. Ann. Rev. Biochem. 51: 238–308.
Reid, I.A., Morris, B.J. and Ganong, W.F. 1978. The renin-angiotensin system. Ann. Rev. Physiol. 40: 377–410.
Unger, T., Ganten, D. and Lang, R.E. 1983. Converting enzyme inhibitors: antihypertensive drugs with unexpected mechanisms. Trends Pharmacol. Sci. 4: 514–519.
Rougeon, F., Chambraud, B., Foote, S., Panthier, J.-J., Nageotte, R. and Corvol, P. 1981. Molecular cloning of a mouse submaxillary gland renin cDNA fragment. Proc. Natl. Acad. Sci. USA. 78: 6367–6371.
Panthier, J.-J., Foote, S., Chambraud, B., Strosberg, A.D., Corvol, P. and Rougeon, F. 1982. Complete amino acid sequence and maturation of the mouse submaxillary gland renin precursor. Nature 298: 90–92.
Masuda, T., Imai, T., Fukushi, T., Sudoh, M., Hirose, S. and Murakami, K. 1982. Molecular cloning of DNA complementary to mouse submandibular gland renin mRNA. Biomed. Res. 3: 541–545.
Imai, T., Miyazaki, H., Hirose, S., Hori, H., Hayashi, T., Kageyama, R., Ohkubo, H., Nakanishi, S. and Murakami, K. 1983. Cloning and sequence analysis of cDNA for human renin precursor. Proc. Natl. Acad. Sci. USA. 80: 7405–7409.
Soubrier, F., Panthier, J.-J., Corvol, P. and Rougeon, F. 1983. Molecular cloning and nucleotide sequence of a human renin cDNA fragment. Nucleic Acids. Res. 11: 7181–7190.
Misono, K.S., Chang, J.-J. and Inagami, T. 1982. Amino acid sequence of mouse submaxillary gland renin. Proc. Natl. Acad. Sci. USA. 79: 4858–4862.
Hirose, S., Kim, S.-J., Miyazaki, H., Park, Y.-S. and Murakami, K. 1985. In vitro biosynthesis of human renin and identification of plasma inactive renin as an activation intermediate. J. Biol. Chem. In press.
Blundell, T., Sibanda, B.L. and Pearl, L. 1983. Three-dimensional structure, specificity and catalytic mechanism of renin. Nature 304: 273–275.
Murakami, K., Hirose, S., Miyazaki, H., Imai, T., Hori, H., Hayashi, T., Kageyama, R., Ohkubo, H. and Nakanishi, S. 1984. Complementary DNA sequences of renin. State of the art review. Hypertension 6: 1-95–I-100.
Akahane, K., Umeyama, H., Nakagawa, S., Moriguchi, I., Hirose, S., Iizuka, K. and Murakami, K. 1985. Three-dimensional structure of human renin. Hypertension 7: 3–12.
Shibanda, B., Blundell, T., Hobart, P.M., Fogliano, M., Bindra, J.S., Dominy, B.W. and Chirgwin, J.M. 1984. Computer graphics modelling of human renin—specificity, catalytic activity and intron-exon junctions. FEBS Lett. 174: 102–111.
Carlson, W., Karplus, M. and Haber, E. 1985. Construction of a model for the three-dimensional structure of human renal renin. Hypertension 7: 13–26.
Evin, G., Devin, J., Castro, B., Menard, J. and Corvol, P. 1984. Synthesis of peptides related to the prosegment of mouse submaxillary gland renin precursor: An approach to renin inhibitors. Proc. Natl. Acad. Sci. USA. 81: 48–52.
Kim, S.-J., Hirose, S., Miyazaki, H., Ueno, N., Higashimori, K., Morinaga, S., Kimura, T., Sakakibara, S. and Murakami, K. 1985. Identification of plasma inactive renin as prorenin with a site-directed antibody. Biochem. Biophys. Res. Commun. 126: 641–645.
Miyazaki, H., Fukamizu, A., Hirose, S., Hayashi, T., Hori, H., Ohkubo, H., Nakanishi, S. and Murakami, K. 1984. Structure of the human renin gene. Proc. Natl. Acad. Sci. USA. 81: 5999–6003.
Hobart, P.M., Fogliano, M., O'connor, B.A., Schaefer, I.M. and Chirgwin, J.M. 1984. Human renin gene: Structure and sequence analysis. Proc. Natl. Acad. Sci. USA. 81: 5026–5030.
Piccini, N., Knopf, J.L. and Gross, K.W. 1982. A DNA polymorphism, consistent with gene duplication, correlates with high renin levels in the mouse submaxillary gland. Cell 30: 205–213.
Panthier, J.-J., Holm, I. and Rougeon, F. 1982. The mouse Rn locus: Sallele of the renin regulator gene results from a single structural gene duplication. EMBO J. 1: 1417–1421.
Mullins, J.J., Burt, D.W., Windass, J.D., McTurk, P., George, H. and Brammar, W.J. 1982. Molecular cloning of two distinct renin genes from the DBA/2 mouse. EMBO J. 1: 1461–1466.
Panthier, J.-J. and Rougeon, F. 1983. Kidney and submaxillary gland renins are encoded by two non-allelic genes in Swiss mice. EMBO J. 2: 675–678.
Panthier, J.-J., Dreyfus, M., Roux, D.T-L. and Rougeon, F. 1984. Mouse kidney and submaxillary gland renin genes differ in their 5′ putative regulatory sequences. Proc. Natl. Acad. Sci. USA. 81: 5489–5493.
Field, L.J., Philbrick, W.M., Howles, P.N., Dickinson, D.P., McGowan, R.A. and Gross, K.W. 1984. Expression of tissue-specific Ren-1 and Ren-2 genes of mice: Comparative analysis of 5′-proximal flanking regions. Mol. Cell. Biol. 4: 2321–2331.
Burt, D.W., Reith, A.D. and Brammar, W.J. 1984. A retroviral provirus closely associated with the Ren-2 gene of DBA/2 mice. Nucleic Acid. Res. 12: 8579–8593.
Ohkubo, H., Kageyama, R., Ujihara, M., Hirose, T., Inayama, S. and Nakanishi, S. 1983. Cloning and sequence analysis of cDNA for rat angiotensinogen. Proc. Natl. Acad. Sci. USA. 80: 2196–2200.
Kageyama, R., Ohkubo, H. and Nakanishi, S. 1984. Primary structure of human preangiotensinogen deduced from the cloned cDNA sequence. Biochemistry 23: 3603–3609.
Doolittle, R.F. 1983. Angiotensinogen is related to the antitrypsin-antithrombin-ovalbumin family. Science 222: 417–419.
Leicht, M., Long, G.L., Chandra, T., Kurachi, K., Kidd, V.J., Mace, Jr., M., Davie, E.W. and Woo, S.L.C. 1982. Sequence homology and structural comparison between the chromsomal human α1-antitrypsin and chicken ovalbumin genes. Nature 297: 655–659.
Tanaka, T., Ohkubo, H. and Nakanishi, S. 1984. Common structural organization of the angiotensinogen and the α1-antitrypsin genes. J. Biol. Chem. 259: 8063–8065.
Travis, J. and Salvesen, G.S. 1983. Human plasma proteinase inhibitors, Ann. Rev. Biochem. 52: 655–709.
Ohkubo, H., Nakayama, K., Tanaka, T. and Nakanishi, S. Tissue distribution of rat angiotensinogen mRNA and structural analysis of its heterogeneity. submitted.
Richoux, J.P., Cordonnier, J.L., Bouhnik, J., Clauser, E., Corvol, P., Menard, J. and Grignon, G. 1983. Immunocytochemical localization of angiotensinogen in rat liver and kidney. Cell Tissue Res. 233: 439–451.
Phillips, M.I. 1983. New evidence for brain angiotensin and for its role in hypertension. Fed. Proc. 42: 2667–2672.
Kageyama, R., Ohkubo, H. and Nakanishi, S. 1985. Induction of rat liver angiotensinogen mRNA following acute inflammation. Biochem. Biophys. Res. Commun. 129: 826–832.
Richards, R.I., Catanzaro, D.F., Mason, A.J., Morris, B.J., Baxter, J.D. and Shine, J. 1982. Mouse glandular kallikrein genes. Nucleotide sequence of cloned cDNA coding for a member of the kallikrein arginyl esteropeptidase group of serine proteases. J. Biol. Chem. 257: 2758–2761.
Swift, G.H., Dagorn, J.-C., Ashley, P.L., Cummings, S.W. and MacDonald, R.J. 1982. Rat pancreatic kallikrein mRNA: Nucleotide sequence and amino acid sequence of the encoded preproenzyme. Proc. Natl. Acad. Sci. USA. 79: 7263–7267.
Fukushima, D., Kitamura, N. and Nakanishi, S. Nucleotide sequence of cloned cDNA for human pancreatice kallikrein. Biochemistry. In press.
Bode, W., Chen, Z. and Bartels, K. 1983. Refined 2Å X-ray crystal structure of porcine pancreatic kallikrein A, a specific trypsin-like serine proteinase. Crystallization, structure determination, crystallographic refinement, structure and its comparison with bovine trypsin. J. Mol. Biol. 164: 237–282.
Chen, Z. and Bode, W. 1983. Refined 2.5Å X-ray crystal structure of the complex formed by porcine kallikrein A and the bovine pancreatic trypsin inhibitor. Crystallization, Patterson search, structure determination, refinement, structure and comparison with its components and with the bovine trypsin-pancreatic trypsin inhibitor complex. J. Mol. Biol. 164: 283–311.
Mason, A.J., Evans, B.A., Cox, D.R., Shine, J. and Richards, R.I. 1983. Structure of mouse kallikrein gene family suggests a role in specific processing of biologically active peptides. Nature 303: 300–307.
Iwanaga, S., Kato, H., Sugo, T., Ikari, N., Hashimoto, N. and Fujii, S. 1979. The Kallikrein-kinin system: A functional role of plasma kallikrein and kininogen in blood coagulation, p. 243–259. In: Biological Functions of Proteinases. Holzer, H. and Tschesche, H. (eds.). Springer-Verlag, Berlin.
Nawa, H., Kitamura, N., Hirose, T., Asai, M., Inayama, S. and Nakanishi, S. 1983. Primary structures of bovine liver low molecular weight kininogen precursors and their two mRNAs. Proc. Natl. Acad. Sci. USA. 80: 90–94.
Kitamura, N., Takagaki, Y., Furuto, S., Tanaka, T., Nawa, H. and Nakanishi, S. 1983. A single gene for bovine high molecular weight and low molecular weight kininogens. Nature 305: 545–549.
Takagaki, Y., Kitamura, N. and Nakanishi, S. 1985. Cloning and sequence analysis of cDNAs for human high molecular weight and low molecular weight prekininogens—Primary structures of two human prekininogens. J. Biol. Chem. 260: 8601–8609.
Furuto-Kato, S., Matsumoto, A., Kitamura, N. and Nakanishi, S. 1985. Primary structures of the mRNAs encoding the rat precursors for bradykinin and T-kinin—Structural relationship of kininogens with major acute phase protein and α1-cysteine proteinase inhibitor. J. Biol. Chem. In press.
Kitamura, N., Kitagawa, H., Fukushima, D., Takagaki, Y., Miyata, T. and Nakanishi, S. 1985. Structural organization of the human kininogen gene and a model for its evolution. J. Biol. Chem. 260: 8610–8617.
Ohkubo, I., Kurachi, K., Takasawa, T., Shiokawa, H. and Sasaki, M. 1984. Isolation of a human cDNA for α2-thiol proteinase inhibitor and its identity with low molecular weight kininogen. Biochemistry 23: 5691–5697.
Kageyama, R., Kitamura, N., Ohkubo, H. and Nakanishi, S. 1985. Differential expression of the multiple forms of rat prekininogen mRNAs after acute inflammation. J. Biol. Chem. In press.
Sueyoshi, T., Miyata, T., Kato, H. and Iwanaga, S. 1984. The primary structure of bovine high molecular weight kininogen: Determination of disulfide linkage sites (Japanese) Seikagaku. 56: 808.
Okamoto, H. and Greenbaum, L.M. 1983. Isolation and structure of T-kinin. Biochem. Biophys. Res. Commun. 112: 701–708.
Anderson, K.P., Martin, A.D. and Heath, E.C. 1984. Rat major acute-phase protein: Biosynthesis and characterization of a cDNA clone. Arch. Biochem. Biophys. 233: 624–635.
Esnard, F. and Gauthier, F. 1983. Rat α1-cysteine proteinase inhibitor. An acute phase reactant identical with α1 acute phase globulin. J. Biol. Chem. 258: 12443–12447.
Cole, T., Inglis, A., Nagashima, M. and Schreiber, G. 1985. Major acute-phase alpha(1)protein in the rat: Structure, molecular cloning, and regulation of mRNA levels. Biochem. Biophys. Res. Commun. 126: 719–724.
Cole, T., Inglis, A.S., Roxburgh, C.M., Hewlett, G.J. and Schreiber, G. 1985. Major acute phase α1-protein of the rat is homologous to bovine kininogen and contains the sequence for bradykinin: its synthesis is regulated at the mRNA level. FEBS Lett. 182: 57–61.
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Nakanishi, S., Kitamura, N. & Ohkubo, H. Structure, Regulation and Evolution of the Genes for the Renin-Angiotensin and the Kallikrein-Kinin Systems. Nat Biotechnol 3, 1089–1098 (1985). https://doi.org/10.1038/nbt1285-1089
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DOI: https://doi.org/10.1038/nbt1285-1089


